USD - US Dollar
EUR - Euro
GBP - British Pound
CAD - Canadian Dollar
AUD - Australian Dollar
CHF - Swiss Franc
SEK - Swedish Kronor
NOK - Norway Krone
DKK - Denmark Krone
JPY - Japanese Yen
ARS - Argentine Peso
NZD - NZ Dollar
PLN - Polish Zloty
SGD - Singapore Dollar
MXN - Mexican Peso
HUF - Hungarian Forint
CZK - Czech Koruna
BRL - Brazilian Real
ZAR - S. African Rand
MYR - Malaysian Ringgit
Free Pills(for all orders with ed pills)
10% Discount(for all next orders)
Free Airmail Shipping(for all orders > $200)
Your cart:
Anti-Depressants
Brandon Van Belle from Belgium
I could not solve my problem with declined transaction via live chat so I had to call them cause I wanted to hear human voice and talk with somebody more competent. Everything was ...
Payton, Perth
“Honeymoon returned and my husband feels like a teenager again. His erection is the same as at our first date 30 years ago. He feels like a man again, his penis is hard with a big ...
Social bookmarks:
Take sick children to pharmacies first, parents told
Visits to GPs and A&E for "self-treatable" conditions cost the service ?850m a year, NHS England says.
Schizophrenia patients calmed by video game
The patients learnt to use the technique in their daily lives to reduce the power of hallucinations.
Peter Rabbit film producers apologise over allergy scene
Sony Pictures "regrets" a scene in the film where bunnies pelt a character with blackberries.
First human eggs grown in laboratory
The feat could lead to new ways of preserving women's fertility.【适用症】
接触性湿疹、异位性皮炎、神经性皮炎、面积不大的银屑病、、扁平苔藓、盘状红斑性狼疮、脂溢性皮炎（非面部）肥厚性瘢痕。
【注意事项】
大面积大量用药或封包方式可使经皮吸收多，可发生全身反应，尤其是低龄儿童和婴幼儿，出现可逆行柯兴氏征及生长迟缓，突然停药可出现急性肾上腺皮质功能不全。出现局部不耐受现象，应停药并寻找原因。警惕留在皮肤皱褶部位和尿布中的药物可吸收入体内。
【用法与用量】
外涂患处每日早晚各一次。
【禁忌症】
对: 过敏者。由细菌、真菌、病毒和寄生虫引起的原发性皮肤病变。溃疡性病变。痤疮、酒渣鼻。眼睑部用药（有引起青光眼的危险）。渗出性皮肤病。
【儿童用药注意事项】
应为面积，短期应用，一旦消退迅速停药，一岁以内儿童尽量不用此药。
【孕妇、哺乳期妇女用药注意事项】
尚无人局部用药致畸作用的研究，妊娠期应慎用。外用经皮吸收大量时可从乳汁排泄，哺乳期慎用。
【不良反应】
少数患者涂药部位的皮肤发生烧灼感、刺痛、暂时性瘙痒，长期应用可发生皮肤毛细血管扩张（尤其面部）、皮肤萎缩、萎缩纹（青少年易发生）皮肤萎缩后继发紫癜、瘀斑、皮肤脆弱、多毛症、毛囊炎、粟丘疹、皮肤脱色、延缓溃疡愈合，封包法在皮肤皱褶部位容易继发真菌感染。经皮肤吸收多时，可发生全身性不良反应。
药理：1．抗炎作用哈西奈德乳膏为局部用药，为高效含氟和氯的皮质类固醇，具有抗炎、抗瘙痒和血管收缩作用。哈西奈德乳膏在去炎松的骨架上，以氯原子取代21位羟基，其血管收缩试验测定抗炎效价倍数为360，已有证据认为血管收缩试验强度与疗效相一致。其抗炎止痒的作用机理是提高β受体对儿茶酸胺的反应性，通过激活腺苷环化酶使cAMP生成增多，并抑制磷酸乙酯酶使cAMP破坏减少，结果使细胞中cAMP年浓度增高，同时又抑制组织胺的释放。哈西奈德乳膏抑制大鼠和小鼠肉芽肿增生的作用与地塞米松相似。用甲醛致小鼠和大鼠后足跟肿胀法观察，哈西奈德乳膏和地塞米松均有明显的抑制作用，而用高5倍量的氢化可的松也无抑制作用。哈西奈德乳膏对胸腺及脾脏有明显的减重作用。2．对各类细胞的选择性药理作用：减少T淋巴细胞、单核细胞、嗜酸性粒细胞数量，抑制淋巴细胞增殖及细胞因子生成，抑制巨噬细胞分化及吞噬活性，抑制中性粒细胞粘附，降低血管内皮细胞通透性，抑制成纤维细胞增殖及胶原合成，抑制皮脂腺细胞活性。3．抗增生作用哈西奈德乳膏具有抗有丝分裂作用，它降低的转录，从而降低DNA的合成，也影响DNA的修复，结果使表皮变薄，尤其对胶原的合成影响最大。4．免疫抑制作用哈西奈德乳膏通过与细胞浆的皮质结合，发生一系列反应，激活了细胞中"基因"的表达；它诱导淋巴细胞中核内DNA裂解直接杀伤淋巴细胞。
【药物代谢动力学】
包括制剂基质、表皮屏障的完整性以及封包等多种因素决定外用哈西奈德乳膏的经皮吸收量。通过正常完整的皮肤也可吸收，炎症性皮肤和或其它皮肤病经皮吸收增加。经皮吸收后其药代动力学的行为与系统应用相同，即不同程度的与血浆蛋白结合，主要肝脏代谢然后从肾脏排泄，也有部分从胆汁排泄。
【拼音名】: HAXINAIDE RUGAO
【性状】: 哈西奈德乳膏为乳白色乳膏。
【包装规格】: 10克/一支，含哈西奈德乳膏0.1%。
【贮藏】: 室温密闭保存。
&|&相关影像
互动百科的词条（含所附图片）系由网友上传，如果涉嫌侵权，请与客服联系，我们将按照法律之相关规定及时进行处理。未经许可，禁止商业网站等复制、抓取本站内容；合理使用者，请注明来源于www.baike.com。
登录后使用互动百科的服务，将会得到个性化的提示和帮助，还有机会和专业认证智愿者沟通。
此词条还可添加&
编辑次数：1次
参与编辑人数：1位
最近更新时间： 19:26:25
贡献光荣榜
扫码下载APP超过900个药物的BCS(BDDCS)分类-共享资料网
超过900个药物的BCS(BDDCS)分类
The AAPS Journal, Vol. 13, No. 4, December 2011 (# 2011) DOI: 10.-011-9290-9Research Article BDDCS Applied to Over 900 DrugsLeslie Z. Benet,1,6 Fabio Broccatelli,1,2 and Tudor I. Oprea3,4,5Received 17 May 2011; accepted 22 June 2011; published online 5 August 2011 Abstract. Here, we compile the Biopharmaceutics Drug Disposition Classi?cation System (BDDCS) classi?cation for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and experimentally measured values. We discuss the potential use of BDDCS to estimate the disposition characteristics of novel chemicals (new molecular entities) in the early stages of drug discovery and development. Transporter effects in the intestine and the liver are not clinically relevant for BDDCS class 1 drugs, but potentially can have a high impact for class 2 (ef?ux in the gut, and ef?ux and uptake in the liver) and class 3 (uptake and ef?ux in both gut and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N =53 compared with over 200 each in classes 1C3). The in?uence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail. KEY WORDS: BDDCS;
permeability rate.In 2005, Wu and Benet (1) introduced the Biopharmaceutics Drug Disposition Classi?cation System (BDDCS). Wu and Benet recognized that there was a very strong correlation between the intestinal permeability rate and the extent of metabolism. For example, Benet et al. (2) noted that for the 29 drugs and endogenous substances for which human jejunal permeability rate measurements were available, there was an excellent correlation between these permeability rate measurements and the extent of drug metabolism in humans. Fourteen of the 16 drugs exhibiting human intestinal permeability rates greater than metoprolol were extensively metabElectronic supplementary material The online version of this article (doi:10.-011-9290-9) contains supplementary material, which is available to authorized users.1Department of Bioengineering & Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, 533 Parnassus Avenue, Room U-68, San Francisco, California , USA. 2 Laboratory of Chemometrics, Department of Chemistry, University of Perugia, Via Elce di Sotto, 10, 60123 Perugia, Italy. 3 Sunset Molecular Discovery LLC, 1704 B Llano Street, Suite 324, Santa Fe, New Mexico 87505, USA. 4 Department of Biochemistry and Molecular Biology, Division of Biocomputing, University of New Mexico School of Medicine, Mail stop code 116145( Albuquerque, New Mexico 87131, USA. 5 Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet, Building 208, Lyngby 2800, Denmark. 6 To whom correspondence should be addressed. (e-mail: leslie. benet@ucsf.edu)olized, while 11 of 12 drugs showing permeability rates less than metoprolol were poorly metabolized. Two drugs showing disparity between the permeability rate and metabolism, cephalexin and losartan, exhibit permeability rates that differ by no more than 16% from metoprolol (2). Since the coef?cients of variation for the human permeability parameters range from 29% to 130%, these borderline compounds may in fact also have followed the correlation. The correlation between the extent of metabolism and human intestinal jejunal permeability was markedly better than that observed for intestinal jejunal permeability and partition coef?cient by Takagi et al. (3), who noted that Log P measured and calculated correctly predict high versus low permeability only about two thirds of the time. Wu and Benet (1) reasoned that it might be easier to utilize metabolism in assigning drug classi?cation since it is dif?cult and expensive to determine human intestinal permeabilities and since it is also dif?cult to obtain quantitative mass balance measures that show ≥90% absorption, the FDA criterion for a biowaiver as de?ned in the FDA BCS Guidance (4), based on the work of Amidon et al. (5). Therefore, in proposing the BDDCS classi?cation system, Wu and Benet (1) substituted extensive and poor metabolism for high and low permeability in the BCS while utilizing the same criteria as the FDA for high and low solubility. That is, a high solubility compound at the highest marketed dose strength would be soluble in 250 mL of water over the pH range of 1C7.5 at 37°C. Using the BDDCS, Wu and Benet (1) classi?ed 168 drugs based on the extent of metabolism and solubility./ # 2011 American Association of Pharmaceutical Scientists519520 BDDCS VERSUS BCS Although BDDCS grew out of the FDA’s BCS Guidance (4), Wu and Benet (1) proposed BDDCS as a means to predict the drug disposition characteristics of novel chemicals (here, referred to as “new molecular entities”, NMEs) during the early stages of drug discovery and development. Such examples will be discussed below. Recently, Benet and Larregieu (6) reviewed the differences between BCS and BDDCS in terms of purpose and basis. The purpose of BCS is to facilitate biowaivers of in vivo bioequivalence studies for drugs that exhibit no signi ?cant intestinal absorption problems. In contrast, the purpose of BDDCS is to predict the drug disposition of NMEs as well as potential drugC drug interactions for NMEs and drugs on the market with respect to the intestine and liver. Very recently, a consensus paper with respect to BCS, BDDCS, and regulatory guidances has been published (7). Both BCS and BDDCS use the same criteria for solubility. Therefore, there is no difference in the basis between the two systems with respect to this parameter. As noted above, BDDCS predictions and classi?cation are based on the intestinal permeability rate, not the extent of permeability. There is some ambiguity with respect to the basis for BCS, as reviewed by Benet and Larregieu (6). The initial permeability studies of Amidon, Lennern?s, and colleagues (5,8), as summarized by Takagi et al. (3), show a good correlation between human intestinal permeability rate and the extent of absorption, as detailed earlier in the ?rst paragraph of this paper. However, the criterion listed in the FDA BCS Guidance (4) is “…a drug substance is considered to be highly permeable when the extent of absorption in humans is determined to be 90% or more of an administered dose based on a mass balance determination or in comparison to an intravenous reference dose” [emphasis added by the FDA]. Although permeability rate methods are listed in the FDA BCS Guidance (4), we are unaware of any drug that has been certi?ed by the FDA as class 1 eligible for in vivo biowaiver where there is no con?rmatory ≥90% absorption data. This ambiguity does not exist in the Guideline on the Investigation of Bioequivalence issued in 2010 by the European Medicines Agency (EMA), which only allows in vivo biowaivers based on the extent of absorption (9). This difference in the permeability basis between BCS and BDDCS is brought home in a recent publication by FDA scientists (10). Chen and Yu (10) note that the FDA has classi?ed as “highly permeable” a number of drugs where absorption is ≥90% in humans, but the measured permeability rates of these compounds are less than that for metoprolol (cefadroxil, cephradine, levo?oxacin, loracarbef, o?oxacin, and sotalol), and in one case (pregabalin), the measured permeability rate is less than that for mannitol. As previously recognized (3), BCS is in?uenced by transporter effects. For example, large amino acid transporter-1 (LAT-1) is expressed in Caco-2 cells (11), and pregabalin is a LAT-1 substrate as noted in the package insert (12), which may explain this discrepancy. Since pregabalin is a zwitterion, its high oral bioavailability (≥90%) may be attributed to LAT-1 transport, an effect that is not taken into account by BCS. Thus, although in general drugs exhibiting high intestinal permeability rates show a high extent of absorption and aBenet, Broccatelli and Oprea high extent of metabolism in both BCS and BDDCS, there are a number of drugs that could be classi?ed as highly permeable in the BCS system based on absorption ≥90% but would be predicted to be poorly metabolized based on the low intestinal permeability rate, the basis for BDDCS classi?cation. By evaluating metabolism, not permeability, BDDCS is not subject to variability due to transporter effects. In general, classi?cation of drugs between BCS and BDDCS only differ about 5C10%. However, for class 1 drugs where FDA has granted biowaivers, we estimate that the difference between BCS and BDDCS occurs for about 40% of drugs. We cannot make a more accurate estimate since the listing of all drugs granted biowaivers by the FDA is con?dential. The percentage difference is high due to the ease in determining whether a drug is &90% absorbed (class 1 in BCS) when a drug is almost completely eliminated unchanged in the urine (class 3 in BDDCS). BDDCS AND ITS USE In 1995, Wu and Benet (1) reviewed 131 drugs that had been classi?ed into the four BCS categories in the literature through the end of 1994. Ten of these drugs had been listed in different classes by different authors. Wu and Benet (1) recognized that the major route of elimination in humans for the great majority of high-permeability class 1 and class 2 drugs was metabolism, while the major route of elimination for the poorly permeable class 3 and class 4 drugs in humans was renal and biliary excretion of unchanged drug. They also noted that the major route of elimination via cytochrome P450 3A4 (CYP3A4) was only observed for the class 1 and class 2 drugs and that for the class 3 and class 4 drugs CYP3A4 was not a major contributor to elimination for any. Since the extent of metabolism is better characterized than the extent of absorption, for marketed drugs, Wu and Benet proposed that in BDDCS, drugs be categorized in terms of the extent of metabolism and solubility versus permeability rate and solubility (1). This immediately eliminated the situation where drugs were classi?ed in more than one class because of the uncertainty of permeability measures from study to study. The implication from the BDDCS for an NME is that if a surrogate measure of intestinal absorption rate is available, such as permeability rate through a Caco-2 cellular system, it would be possible to predict the major route of elimination for this new molecular entity in humans prior to its in vivo dosing to either animals or humans. Work is ongoing in our laboratory to determine the degree of accuracy in predicting BDDCS class for an NME based only on in vitro permeability measures prior to studies determining the extent of metabolism. Thus, Benet and Wu (1) proposed the BDDCS as shown in Fig. 1 with ≥70% metabolism being the cutoff for extensive metabolism. They also noted that there were relatively few drugs where the extent of metabolism was between 30% and 70% and that most drugs are either very highly metabolized or very poorly metabolized. Figure 2 summarizes the predictions from BDDCS related to the effects of enzymes and transporters in the gut and liver following oral dosing of drugs (1,13). For class 1, highly soluble―high permeability rate―extensively metabolized drugs, transporter effects in the intestine and the liver have no clinical impact. Even compounds like verapamil,BDDCS Applied to Over 900 Drugs521 hepatocyte, ef?ux transporter effects can also occur. Similarly, uptake and ef?ux transporter effects would be expected for the poorly soluble class 4 compounds. Because they are numerically underrepresented, one might expect that class 4 drugs are more dif?cult to manage therapeutically, i.e., there are transporter effects just as in class 2, except these drugs are not signi?cantly metabolized. As will be shown subsequently, plotting the maximum recommended therapeutic daily dose (14) versus BDDCS and looking at the “actives” (low dose) versus “inactives” (high dose, safer) revealed no such relationship. It is more likely that fewer drugs are represented in class 4 because of the combined negative characteristics of high dose and (comparatively) low solubility, which leads to high variability. Since the FDA criteria for solubility is measured in water, we suspect that the approved class 4 drugs have adequate solubility in the natural surfactant containing intestinal ?uids. Details and explications for the predictions in Fig. 2 have been presented in recent reviews from the Benet lab (13,15,16). However, in large part, the predictions in Fig. 2 were based on clinical and experimental observations. That is, we are unaware of any clinically signi?cant effects of the uptake and ef?ux transporters in the gut and liver on class 1 drugs, even when such drugs have been shown in cellular systems or other organs besides the gut and the liver to be substrates of the uptake and ef?ux transporters. These effects, however, might become relevant in overdosage situations, e.g., when combined with strong inhibitors of their respective metabolizing enzyme, when liver failure is manifest, or when accidentally overdosed. Similarly, we are unaware of the clinically signi?cant effects of the uptake transporters in the gut for class 2 drugs even when these drugs are shown to be substrates of uptake transporters in the liver. BDDCS also allows potential drugCdrug interactions to be predicted (16,17). For class 1 drugs, only metabolic interactions need to be considered in the intestine and the liver. For class 2 drugs, metabolic, ef?ux transporter, and ef?ux transporterCenzyme interplay in the intestine must be taken into consideration, while in the liver, metabolic, uptake transporter, ef?ux transporter, and transporterCenzyme interplay (both uptake and ef?ux) can occur. For class 3 and class 4 drugs, uptake transporter, ef?ux transporter, and uptakeCef?ux transporter interplay will be of major importance. BDDCS classi?cation may also be useful in predicting the effect of high-fat meals on the extent of bioavailability (F) for an NME. In general, F for class 1 drugs is unaffected by high- F is generally increased for class 2 drugs and generally decreased for class 3 drugs (18). Custodio et al. (19) have observed that these ?ndings would be the outcomes expected if a component of high-fat meals inhibited both the uptake and ef?ux transporters. However, even if this were true, high-fat meals would be expected to have many other effects than inhibiting transporters. We estimate that the predicted effect of high-fat meals on F is only correct about 70% of the time. CAUTION It is surprising that such a simple four-category process as indicated in Fig. 2 works so well in predicting drug disposition, transporterCenzyme effects, and drug interac-Fig. 1. The Biopharmaceutics Drug Disposition Classi?cation System (BDDCS) as proposed by Wu and Benet (1)which can be shown in certain cellular systems (e.g., MDR1MDCK) to be a substrate for P-glycoprotein (P-gp), exhibit no clinically signi?cant P-gp substrate effects in the gut and the liver. Thus, a major proposition of BDDCS is that although class 1 drugs may be shown in cellular systems to be substrates for transporters found in the intestine and the liver, this has no clinical relevance. However, a caution is in order here. At this time, BDDCS predictions only apply to the intestine and the liver since class 1 drugs could be substrates for transporters at the bloodCbrain barrier and in the kidney. From Fig. 2, it can be seen that for class 2 drugs, ef?ux transporter effects will predominate in the intestines. Thus, transporterCenzyme interplay will be primarily important for class 2 compounds that are substrates for CYP3A and phase II gut enzymes (e.g., glucuronosyltransferases, sulfotransferases), where ef?ux transporter effects can control the access of the drug to the gut enzymes. BDDCS predicts that both uptake and ef?ux transporters can affect class 2 drug disposition in the liver. Thus, inhibition or induction of uptake hepatic transporters such as the SLCOs (OATPs) and the SLC22As (OATs and OCTs) as well as the drug ef?ux hepatic transporters ABCB1 (P-gp), ABCG2 (BCRP), and ABCCs (MRPs) can lead to changes in hepatic metabolism even when hepatic enzymes are unaffected. BDDCS predicts that for class 3, highly soluble―poor permeability rate―poorly metabolized drugs, uptake transporters will be important for intestinal absorption and liver entry for these poorly permeable compounds (Fig. 2). However, once these drugs get into the enterocyte or theFig. 2. Transporter effects predicted by BDDCS following oral dosing522 tions. It is obvious, however, that this simple four-category system will not predict every interaction. BDDCS does not propose that every drug in the class will be substrates or not substrates for the uptake and ef?ux transporters. Rather, BDDCS helps prioritize what interactions should and should not be investigated. For example, the class 2 drug felodipine has been shown not to be affected by the intestinal or hepatic ef?ux transporters (20). Recently, our laboratory has shown the importance in humans of hepatic uptake transporters for the drugs atorvastatin and glyburide (21,22). These interactions were predicted based on cellular, isolated organ, and animal studies (22C24). Even when such preliminary studies con?rm BDDCS predictions, this may not always be the case. Warfarin is a class 2 drug and, thus according to BDDCS, may be a substrate for a hepatic uptake transporter. In vitro studies in human and rat hepatocytes showed that rifampin would decrease warfarin metabolism by 30% (25), a similar extent to that found for our in vitro results with glyburide (22). However, our recently published study examining the effects of a single dose of rifampin on the pharmacokinetics of warfarin in healthy volunteers showed that OATP uptake in vivo in humans was not clinically signi?cant for warfarin (25). Similarly, although warfarin appears to be both a substrate and inhibitor of liver-bound P-gp (26), this has not been regarded as clinically signi? one P-gp haplotype, however, is clearly associated with low-dose warfarin in a 201 patient sample (27). This emphasizes again the caution that BDDCS only predicts with respect to transporters what might occur, but not that the effect will always occur. Furthermore, our example above (25) reinforces the well-recognized concept that observations in cellular systems and animal models must be tested in vivo in humans before the signi?cance of the effect is assumed. WHY DID WE PREPARE THIS PAPER? Wu and Benet (1) recognized that the FDA’s BCS approach (4) held the potential for predicting the drug disposition characteristics and drug interactions for NMEs as well as for drugs on the market. The use of BDDCS in the area of systems chemical biology (28) has been previously outlined (29), and computational models to assign BDDCS class from molecular structure have been proposed (30). However, to test the usefulness of BDDCS, to examine patterns within the BDDCS classes and among them, and to gain further perspectives, it is necessary to compile a large database, at least with respect to drugs that have reached the market. Since BDDCS makes predictions related to hepatic elimination in addition to intestinal absorption, such a database should include as many drugs as possible where systemic concentrations are relevant. Thus, approximately one quarter of the drugs categorized here are administered exclusively by non-oral routes. We also felt strongly that the information provided in the database should be based, where available, not only on the in silico predictions of those parameters but also on experimental values. We noted that many of the solubility values used in BCS analyses are frequently in silico predictions of solubility. For example, in the often quoted paper of Willmann et al. (31) describing a physiological model for the estimation of the fraction dose absorbed in humans, the measured solubility values were only included for only 22Benet, Broccatelli and Oprea of the 126 drugs evaluated. The solubility for the great majority of the drugs utilized in the Willmann et al. (31) analysis came from the compilation of Zhao et al. (32). These latter workers evaluated human intestinal absorption data for 241 drugs (32). Of the 241 drugs, Zhao et al. compared the experimental results for 26 of the compounds with the predicted solubility utilizing the method of Meylen et al. (33) based on octanol water partition coef?cients. For these 26 drugs, the measured versus calculated solubility differs by a factor of 5.7±6.0-fold, the greatest difference being 23-fold. Thus, at present, in silico methodologies for aqueous solubility prediction are not suf?ciently accurate for the BDDCS analysis not only due to the inherent limitations of such methods but also to its de?nition, i.e., BDDCS solubility categorization depends on the maximum strength dose and the effect of pH. Experimental solubility values were included in this compilation wherever they could be found in the literature (577 drugs). Qualitative evaluations such as “practically insoluble in water,” which relate to upper limits, and “highly soluble in water” were used in the absence of published solubility values from a reliable source and were the basis of the BDDCS assignment when no measured value is listed in the table. Frequently, large compilations such as the ones presented here are carried out with the assistance of graduate students, postdoctoral fellows, and auxiliary personnel. In our experience, this can lead to unevenness in the quality of the data presented in the table. For each of the drugs listed here, decisions concerning the experimental values to be listed and classi?cation assigned were made during the multiple joint meetings of Drs. Benet and Oprea between February 2007 and February 2011. Then, Dr. Broccatelli captured potential errors by cross-checking many references. Therefore, if there are errors in the parameters or in the assignments, this can only be attributable to the authors. MEASURED PARAMETERS (IN ORDER OF DIFFICULTY) Solubility There are a number of issues concerning the choice of the high versus low solubility criteria and which representative experimental values should be listed. The high solubility criterion that the highest dose strength on the market is soluble in 250 mL or less of water over the pH range 1C7.5 at 37°C was an arbitrary decision made by Amidon et al. (5) and incorporated into the regulatory Guidances (4,9). Wu and Benet (1) found that this cutoff criterion in BCS appeared to work well for BDDCS, and thus, we have continued to use this arbitrary, discriminatory criterion. The FDA criteria (4) require the solubility measurements to be made in water, not simulated intestinal ?uid containing a surfactant, and the solubility values listed in the table are values in water. Furthermore, the FDA criteria evaluate the cutoff between high and low solubility using the value for the lowest solubility over the pH range 1C7.5 (realistically measured at pH 1.2, 4.5, and 6.8 as indicated in the FDA Guidance). Furthermore, the solubility is to be measured at 37°C. The values in Tables I, II, III, IV, and V are the authors’ best recommendation based on experimental literature data forTable I. Measured and In Silico Data for 351 BDDCS Class 1 DrugsGeneric name Formulation MW drug ?0.57 1.20 77 0.02 1.2 1 10 3 Route CLogP HBAMaximum strength dose value Measured solubility (mg/mL) Dose number Measured LogS molar Measured LogP Measured LogD74 % Excreted unchanged in urine minVSLgS 3C7.5 HBDMaximum strength dose unitPSA0.2 0.6 0.2(i.v.) (i.v.) 2.16 2.10 ?1.18 2.45 1.26 1.34BDDCS Applied to Over 900 Drugs23.7 3.43 10 5?0.80 ?1.98 ?1.26 ?1.731.20 ?8.83 1.71 0.20 2.44 1.19 ?0.98 0.19 0.40 ?0.36 ?2.57 ?1.10350 61 0.073 50 0.06 10.9 2.12 3.10 (i.v.) 55.55
0.02 0. 0.50 ?1.04 4.92 3.00 1.00 2.95 1.680.003 0. 0.02 0.7 0.011.4 0 8 0.5 11 25 6 20 0.5 5 8 0.69 ?0.20 ?0.68 ?3.63 ?0.70 ?3.80 ?1.52300 100 400
3 1 0.5 10 300 1 2 200 10 30 5 300 150 10 150 33.33 1 1 (i.v.) (i.v.) .001 0. 10 0.008 0. 0.5 ?2.77 ?1.90 3.70 3.69 0.28 2.30 0.96 ?1.13mg mg mg mg mg mg mg/mL μg mg/mL mg mg mg mg mg mg mg mg/mL mg mg mg mg mg/mL mg mg/mLTablets Tablets Capsules Tablets Tablets Tablets Solution Capsules Solution Tablets Tablets Tablets Tablets Tablets Tablets Tablets Solution Tablets Tablets Tablets Tablets Solution Tablets SolutionOral Oral Oral Oral Oral Oral Injection Oral Injection Oral Oral Oral Oral Oral Oral Oral Injection Oral Oral Oral Oral Injection Oral Injection286.34 645.62 336.43 151.17 324.40 180.16 267.25 400.65 416.53 389.46 551.77 294.36 308.77 249.36 376.46 364.08 214.22 231.30 277.41 408.89 313.79 393.47 293.37 792.98?3.07 3.30 ?1.46 ?1.66 ?3.13 ?0.94 ?1.37 ?5.86 ?4.12 ?3.80 ?3.09 ?3.26 ?3.68 ?0.86 ?3.35 ?2.44 3.12 ?2.23 ?2.29 ?1.79 ?2.43 ?1.37 ?3.60 ?7.12 0.81 ?6.66 1.71 0.49 2.25 1.02 ?2.16 8.24 2.13 2.55 3.51 1.74 2.56 2.65 3.33 2.66 ?1.85 1.04 4.85 3.43 3.41 4.69 1.29 6.11 6 19 5 2 4 3 8 2 6 8 7 2 3 3 5 3 5 3 1 5 3 5 4 83 14 3 2 2 1 4 2 0 2 4 1 0 2 1 3 4 0 0 2 1 2 0 295.80 351.80 97.05 55.41 103.22 68.21 135.44 45.12 77.73 108.88 156.62 44.23 33.27 46.24 70.11 64.50 106.66 26.79 1.18 105.47 34.47 85.11 61.36 130.0527.8 10 33 78 1.9 0.020.009 0.04 0.002 0.002?0.96 ?1.44 ?1.05 ?0.74 ?2.450.5 0.3 1 1.5 1 0 0.5 1 1 1 0.5 4.8 150.10 1.500.02 ?2.58 1.101.0 0.3 0..3 0.2 0.008 0.0022.00 1.94 2.81 4.25 0 10 0.1 0.03 0.4 0.6 4.22 0.78 2.05 2.74 3.20 1.94 0.550.4 5 19 0.066 0.451 0.8 1 3.3 3.3 1.5 0.17 0.8 0.09 0.02 0.17 17 312 0.1?2.81 ?1.87 ?1.32 ?3.77 ?2.83 ?2.72 ?2.49 ?2.06 ?2.07 ?2.29 ?3.27 ?2.91 ?3.67 ?4.331.54 4.59 3.34 2.70 ?0.75 0.002 0.001 0.08 2 0.5 0 23.6 2 1 0.5 1 ?3.23 ?1.47 0.11 ?3.39 3.41 4.98 ?0.52 3.27 ?0.52Abacavir sulfate Acarbose Acebutolol hydrochloride A paracetamol Acetohexamide A aspirin Adenosine Alfacalcidol Alfentanil Alfuzosin Aliskiren Alosetron Alprazolam Alprenolol Ambrisentan Ambroxol Amifostine A aminopyrine Amitriptyline hydrochloride Amlodipine Amoxapine Amsacrine Anastrozole A anhydrovincaleukoblastine A phenazone Apomorphine Asenapine Atomoxetine Azathioprine Bambuterol Benazepril Bendamustine Benidipine Benserazide Benznidazole Bepridil Beraprost Betamethasone Betaxolol Bimatoprost Biperiden Bopindolol Bortezomib Brimonidine Bromazepam Bromocriptine Bromperidol Budesonide Bu?omedil hydrochloride Bupivacaine Buprenorphine hydrochloride Bupropion Busulfan (busulphan) Tablets Tablets Tablets Capsules Tablets Tablets Tablets Solution Tablets Tablets Tablets Tablets Tablets Tablets Tablets Solution Tablets Tablets Solution Solution Tablets Capsules Tablets Capsules Tablets Solution Tablets Tablets Tablets Oral Injection (s.c.) Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Oral Oral Oral Ophthalmic Oral Oral Injection (i.v.) Ophthalmic Oral Oral Oral Oral Oral Injection (epidural) Oral Oral Oral 188.23 267.33 285.78 255.36 277.27 367.45 424.50 358.27 535.65 257.25 260.25 366.55 398.50 392.47 307.44 415.58 311.47 380.49 384.25 292.14 316.16 654.61 420.33 430.55 307.39 288.44 467.65 239.75 246.30 ?1.79 ?2.73 ?2.41 ?1.14 ?2.72 ?1.56 ?1.84 ?0.83 ?5.69 2.13 ?2.65 ?4.29 ?4.64 ?3.61 ?1.66 ?5.44 ?1.93 ?3.92 ?4.09 ?2.00 ?3.47 ?6.80 ?3.84 ?4.71 ?1.23 ?3.53 ?3.58 ?1.99 ?1.20 0.20 2.49 4.58 3.94 0.51 0.56 1.82 2.76 7.41 ?2.90 0.90 6.20 2.04 1.79 2.32 1.75 4.94 4.98 0.78 1.49 1.70 6.58 4.00 2.91 2.93 3.69 3.99 3.21 ?0.59 2 3 1 2 6 4 5 4 0 7 4 3 5 5 4 4 2 3 6 5 3 6 3 6 5 2 5 2 4500 2.56 10 60 100 20 40 5 8 50 100 400 0.04 5 20 0.30 2 2 1 2 6 5 10 3 300 5 8 100 2mg mg mg mg mg mg mg mg/mL mg mg mg mg mg mg mg mg/mL mg mg mg/mL mg/mL mg mg mg mg mg mg/mL mg mg mg0 2 0 1 1 2 2 1 0 7 1 0 3 3 2 4 1 2 4 2 1 3 1 2 0 1 2 1 022.02 46.92 10.59 23.68 99.66 94.24 101.61 69.78 112.85 169.84 87.81 10.84 95.05 104.22 55.03 100.52 23.73 64.71 151.53 58.94 52.40 118.24 42.01 99.25 46.76 33.72 64.50 32.84 92.04523524Table I. (Continued)Generic name Formulation MW drug Route CLogP HBAMaximum Maximum strength strength dose value dose unit Measured solubility (mg/mL) Dose number Measured LogS molar Measured LogP Measured LogD74 % Excreted unchanged in urine minVSLgS 3C7.5HBDPSA1.65 2.26 ?0.07 ?0.07 ?2.21 ?0.96 ?1.141.45Butabarbital Butalbital Butorphanol Caffeine Capecitabine Caprylidene Carbidopa Carmustine 2 21.5 26 2.5 3.8 1.53 1.53 0.04 0.008 ?1.96 ?1.75 0.01 0.01 0.08100 50 5 65 500 .70mg mg mg mg mg mg mg mgTablets Tablets Tablets Caplets Tablets Powder Tablets Implant1 3.6 2 1 3 0 5.3 0.5212.25 224.26 327.47 194.19 359.36 470.70 226.23 214.05?2.42 ?2.74 ?2.40 ?1.95 ?3.45 ?7.69 1.33 ?2.50 1.58 1.63 3.73 ?0.04 0.84 9.97 ?0.45 1.323 3 3 3 6 3 6 22 2 2 0 3 0 5 183.96 83.96 46.61 48.50 124.33 81.19 132.39 69.78?0.74 ?0.37 ?2.25 1.70 ?1.40 ?2.11 ?2.18 ?1.21 0.99 3.25 1.14 2.44 2.12 3.38 5.41?2.12195 8 .5 2 10 0.002 0.02 0.003 0.03 0.2 0.2 0.08 5.7 8 0.5 0.5 1 0.1 0.7 0.4 0.05 0.080.000021.4 29 24 3 13.5 1.61 1.59 1.00 2.19 2.12 1.38 2.82 ?2.25 0.10 ?2.62 ?2.07 ?2.17 ?1.08 ?3.20 ?0.68 ?2.73 ?3.50 ?2.53 5.49 2.16 3.046.48
3 30 500 2 250 25 192 4 200 5 1 2 300 400 1 2.53 2.3 40 0.188 45 1.11 0.1 0.5 5 0.5 0.05 10 0.5 0 2.3 5 13 Tablets Oral 2.12 2.57 6.70 5.19 2.41 2.30 1.19 1.30 1.47 1.90 ?1.13 2.76 2.41 ?1.13 2.30 0.21 1.03 1.47mg/mL mg mg mg/mL mg mg mg mg mg mg mg mg mg mg/mL mg mgSolution Powder Tablets Solution Capsules Capsules Tablets Capsules Capsules Capsules Tablets Tablets Tablets Solution Tablets CapsulesOral Oral Oral Oral Oral Oral Oral Topical (skin, membranes) Injection (i.v.) Injection (i.v.) Oral Injection (s.c.) Oral Oral Oral Oral Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral .68 459.56 .32 165.40 304.22 323.13 299.76 161.65 274.80 318.87 417.51 300.06 343.90 424.99 ?3.18 ?3.47 ?2.00 ?7.00 ?1.32 ?0.77 ?0.27 ?2.79 ?2.65 ?1.80 ?1.57 ?2.69 ?0.78 ?2.56 ?2.99 ?2.95 ?0.22 3.56 ?0.40 1.14 0.72 3.63 1.28 3.79 1.68 3.15 5.30 1.47 ?1.68 5.45 2.5718 11 6 18 2 2 3 5 3 1 2 2 6 0 2 616 4 3 17 0 2 1 3 1 0 0 0 2 2 0 4454.42 227.75 104.98 543.33 9.97 45.12 41.70 122.11 45.94 10.24 11.42 1.75 106.36 75.29 9.97 110.49101.6 435 45 0.28 12.5 8.7 200 40 3.636 1.8 2 29 0.2 0.2 0.0030.05 0.4 0.002 0.02 0. 0.004?2.28 0.14 ?0.95 ?3.11 ?2.04 ?1.49 ?0.14 ?0.81 ?1.900.63 ?2.24 ?2.54 ?2.20 ?0.78 0.7750 75 2 15 0.1 60 0.6 25 5 50 10 50 4 20 110 100 15 20 Tablets Tablets Tablets Tablets Tablets Oral Oral Oral Oral OralTablets Tablets Tablets Tablets Solution Tablets Tablets Tablets Tablets Tablets Tablets Tablets Tablets Solution Capsules Capsules Tablets TabletsOral Oral Oral Oral Topical (nasal) Oral Oral Oral Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral0.63 4.69 ?2.51 3.80 1.70200 10mg Active metabolite mg mg mg mg mg/mL mg mg mg mg mg mg mg mg mg/mL mg mg mg mg Active metabolite mg mg 0.057 0.32 0.092 0.7 0.02 0.03 0.5 0.5 0.5 6.5 0.5 11 0 5 12.5 12 0.5 2 0.5 0 2.6 0.5300.75 214.65 405.97 314.86 315.72 314.73 303.36 299.37 399.45 360.45 .39 275.40 261.09 287.41 243.22 627.75 314.26 426.56 175.24 288.71 266.39 270.72 310.48 392.47 233.31?3.68 ?2.99 ?3.63Caspofungin acetate Cefoperazone Cerivastatin Cetrorelix Cevimeline Chloral hydrate Chlorambucil Chloramphenicol Chlordiazepoxide C clomethiazole Chlorpheniramine Chlorpromazine Cilazapril Cisplatin Clemastine Clindamycin hydrochloride hydrate Clobazam Clo?bric acid Clomiphene citrate Clomipramine Clonazepam Clorazepate Cocaine Codeine monohydrate Colchicine Cortisone Cyanocobalamin (vitamin B12) Cyclizine Cyclobenzaprine Cyclophosphamide Cyproheptadine Cytarabine Dabigatran etexilate Dantrolene Darifenacin Debrisoquine Desalkyl?urazepam Desipramine Desmethyldiazepam (nordazepam) Desogestrel Dexamethasone Dexmethylphenidate 0.75 2.70 4.90 2.93 ?2.96 2.78 1.40 2.93 1.94 1.80 1.83 ?0.28?3.63 ?1.63 ?4.24 ?2.56 ?3.96 ?2.36 ?2.85 ?1.40 ?3.90 ?3.52 0.05 ?2.97 ?2.58 ?1.92 ?3.19 ?0.60 ?7.74 ?3.44 ?3.74 2.59 ?3.78 ?0.80 ?3.69 ?4.86 ?3.65 ?1.612.44 2.82 7.15 5.92 2.38 2.51 2.57 0.98 1.20 1.30 ?1.36 3.80 5.10 0.80 5.30 ?2.20 4.13 1.63 3.62 0.90 2.81 4.47 3.02 5.68 1.79 2.562 3 2 2 4 4 3 4 6 5 17 2 1 2 1 7 8 5 3 3 2 2 2 1 5 20 1 0 0 1 2 0 1 1 2 9 0 0 1 0 4 2 1 1 2 1 1 1 1 3 137.99 49.94 10.28 1.75 86.30 82.98 55.30 41.94 87.54 99.93 492.69 2.35 1.18 44.31 1.18 133.23 146.19 118.74 56.52 52.16 42.15 15.14 42.15 22.56 104.22 41.64Benet, Broccatelli and Oprea1.5 0.75 10mg mg mg60 Solution Tablets Tablets Tablets 0.7 0.02 0.1 ?1.31 0.59 3.09 2.70 3.27 1.07 2.22 1.61 2.82 4.51 3.44 16 2 Injection (i.v.) Oral Oral Oral 20 0.057 9 11.1 1 0.5 0.5 18 245.37 284.75 296.16 326.44 ?1.09 ?3.70 ?1.52 ?1.51 1.12 2.99 1.13 1.82 3.72 2.96 4.73 3.27 2 2 3 6 2 0 2 3 ?0.65 ?3.75 ?3.43 ?2.61 50.84 28.76 54.80 43.08mgTabletsOral150.020.19271.41?1.26 3.95 2 0 10.28?1.3515 10 50 300mg/mL mg mg mg5002.5 2 2 0.1 0 5 0.23 4.49BDDCS Applied to Over 900 Drugs10 4 25
?1.51 ?2.82 3.69 0.46 2.85 10 2 20 0.5 0.09 0.2 0.09 0. 0.04 0.003 ?1.98 ?1.18 ?0.65 1.100 3.5 0 5 10 0 9.5 ?1.744.29 1.272.76 0.60 2.37 1.27?2.09 ?3.77 ?1.84 ?1.85 ?1.96 ?2.26 ?4.55 ?2.30 ?3.74 ?2.22 ?2.30 ?0.67 2.50 3.65 3.45 2.43 2.34 4.53 3.53 4.09 0.32 4.26 3.36 0.67?1.17 ?2.84 ?3.482.23 4.01 ?0.31 3.67 0.38 ?0.31 3.67 1.13Dextromethorphan hydrobromide Dezocine Diazepam Diclofenac D hydroquinidine Dilevalol Diltiazem Diphenhydramine Dobutamine hydrochloride Dolasetron D dothiepin Doxazosin Doxepin Doxorubicin Duloxetine hydrochloride Eletriptan hydrobromide Enalapril Enfuvirtide Epirubicin E ergometrine Ergotamine tartrate Escitalopram Esmolol Esomeprazole magnesium Estradiol Eszopiclone Ethanol Ethinylestradiol Ethosuximide Etonogestrel 39.2 0.51 0.4 0 0.03 0.001 8 0.5 0.5 0.5 5 2.5 3 25 0.1 ?0.56 ?2.80 328.41 414.53 255.36 301.39 324.38 295.45 451.49 279.39 543.53 297.42 382.53 376.46 .53 325.41 581.68 324.40 295.38 345.42 272.39 388.82 46.07 296.41 141.17 324.47 ?3.77 ?3.07 ?2.74 ?2.94 ?0.80 ?3.69 ?3.90 ?2.82 1.06 ?4.16 ?1.24 ?4.61 ?8.68 0.32 1.23 4.66 3.13 1.72 2.57 3.78 1.25 ?0.24 3.86 0.40 5.68 4 4 2 4 3 1 9 2 12 2 3 5 67 12 3 6 3 4 5 2 6 1 2 2 2 4 0 0 4 1 0 1 0 6 1 1 2 63 6 3 3 0 2 1 2 0 1 2 1 1 106.25 56.49 9.97 83.19 60.48 1.18 104.90 10.28 222.89 23.68 51.90 101.91 .89 70.55 118.24 28.67 73.30 71.04 45.43 79.29 22.56 45.43 51.12 22.5650 120 50 12.5 100 75 8 100 2 67.3 40 20 90 2 0.2 2 20 10 20 2 3 62 1 250 157mg mg mg mg/mL mg mg mg mg mg/mL mg mg mg mg/mL mg/mL mg mg mg mg/mL mg mg mg mg/mL mg mg μg1 0.25 500 1.6 8 5 0.008 0.1 0.5 0.01 0.003 1.0 0 8 0 0.5 24 Tablets Oral 3.53Tablets Capsules Capsules Solution Tablets Tablets Tablets Capsules Solution Capsules Tablets Tablets Solution Solution Tablets Tablets Tablets Solution Tablets Tablets Tablets Solution Tablets Capsules Tablets (and 68 mg implant s.c) Tablets Solution Tablets Lozenge Tablets Tablets 0.01 25 250 25 256 0.043 ?4.98 ?2.22 ?0.11 ?1.13 ?0.21 ?3.94 958.25 .34 336.48 411.59 372.56 285.24 365.22 ?2.01 1.67 1.00 2.06 ?0.89 4.05 3.94 3.80 1.12 0.005 0. 0.03 0. 0.87 2.06 ?0.89 1.95 2.35 1.21 0.95 10 15 0.2 100 11 50 0.005 0.5 0. 1 0.5 0.5 5 1.25 0.1 1.5 2 8 ?3.48 ?3.37 ?4.89 ?1.03 ?1.31 0.11 ?0.92 ?1.33 ?2.72 0.14 0.128 0.004 12.2 15.2 500 50 14.869 0.66 4.05 3.03 ?0.80 2.92 3.03 ?2.32 ?2.79 ?3.65 ?1.83 ?4.38 ?1.68 0.64 7.10 1.61 0.09 3.62 4.36 3.01 ?2.01 ?3.07Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Injection (i.m.) Injection (i.v.) Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Oral Oral Topical (skin. membranes) Oral Injection (s.c.) Oral Oral Oral Oral10mg mg/mL mg mg mg mg Active metabolite mg13 67 6 2 3 2 8 83 58 1 0 1 2 4 4212.97 .10 20.32 51.11 65.69 135.44 185.94Everolimus Exenatide Famciclovir Fentanyl Fesoterodine Finasteride Fludarabine Fludarabine 5′-monophosphate Fludrocortisone acetate Flumazenil Flunitrazepam Fluorouracil Fluoxetine Flurazepam Fluvastatin sodium Fluvoxamine Formoterol fumarate Fos?uconazole Frovatriptan Galantamine Gemcitabine hydrochloride Glibornuride Goserelin Granisetron Guanabenz H enoxaparin Tablets Solution Tablets Solution Capsules Capsules Capsules Tablets Powder Tablets Tablets Tablets Solution Tablets Implant Tablets Tablets Solution (10,000 units/mL) Oral Injection (i.v.) Oral Injection (i.v.) Oral Oral Oral Oral Topical (aerosol) Oral Oral Oral Injection (i.v.) Oral Injection (s.c.) Oral Oral Injection (i.v.) 6 20 8 0.5 20 11 0.5?1.46 ?1.24 ?3.26 ?0.49 ?1.32 ?1.362.603.53 ?0.85 0.120.1 0.1 1 25 20 30 40 100 12 100 2.5 12 40 25 10.8 1 16 20mg mg/mL mg mg/mL mg mg mg mg μg/inhalation mg mg mg mg/mL mg mg mg mg mg/mL422.50 303.30 313.29 130.08 309.33 387.89 411.48 318.34 344.41 386.26 243.31 287.36 263.20 366.48 .42 231.09 1134.94?4.00 ?3.34 ?3.53 ?0.62 ?1.19 ?3.52 ?4.00 ?1.68 ?2.00 2.41 0.42 ?1.09 ?0.97 ?3.75 ?5.55 ?1.16 ?1.38 ?3.811.54 1.29 1.78 ?0.58 4.57 4.22 4.05 3.32 1.26 ?0.78 0.72 1.03 ?0.71 3.70 ?2.86 1.72 2.98 ?9.695 3 4 2 2 3 4 4 5 7 2 4 6 4 18 3 4 332 0 0 2 1 0 3 1 4 2 3 1 3 3 18 1 3 15104.22 57.02 72.91 64.48 23.68 29.93 86.52 58.37 101.65 120.98 74.79 41.94 110.67 107.50 537.10 47.74 78.44 662.73525526Table I. (Continued)Generic name Formulation MW drug Route CLogPMaximum Maximum strength strength dose value dose unit Measured solubility (mg/mL) Dose number Measured LogS molar HBA Measured LogP Measured LogD74 % Excreted unchanged in urine minVSLgS 3C7.5HBDPSA250 100 10 20 8 200 6 27 1.72 3.50 2.37 0.27 ?0.58 700 100 100 1 0. ?2.60 ?2.49 ?0.70 2.09 ?0.42 ?2.56 0.86 2.97 1.63 0.86 0.46 2.20 Tablets Solution Solution Solution Solution Tablets Tablets Cream 0.6 0.9 0.02 25 187.20 Solution 0. 7 3 10 0 5 1.5 1 374.91 384.59 497.51 261.09 360.50 405.45 280.42 240.31 ?3.76 ?2.01 ?3.81 ?2.40 ?4.40 ?0.68 ?2.04 ?2.71 ?1.89 4.00 3.78 0.90 0.92 2.71 1.53 5.04 3.24 ?0.69Hexobarbital Hydralazine hydrochloride Hydrocodone H cortisol Hydromorphone Hydroxychloroquine sulfate Hydroxyzine Ibutilide Idarubicin Ifosfamide Iloprost Imidapril Imipramine Imiquimod Oral Injection (i.v.) Injection (i.v.) Injection (i.v.) Topical (aerosol) Oral Oral Topical (skin. membranes) Injection (i.v.)mg mg mg mg mg mgTablets Tablets Tablets Tablets Tablets TabletsOral Oral Oral Oral Oral Oral640 44.2 62.5 0.42 10 2000.002 0.009 0. 0.003 0.0040.5 8 10.2236.27 160.18 299.37 362.47 285.35 335.880.43 ?0.65 ?0.68 ?2.94 ?1.46 ?0.231.98 1.00 1.27 1.611.98 0.56 3.38 1.37?2.81 ?1.29 ?1.25 ?3.48 ?1.06 ?1.64 1.63 0.66 1.13 1.70 0.72 4.123 4 4 5 4 4 4 4 10 2 4 6 2 3 31 2 0 3 1 2 1 2 5 1 3 2 0 1 270.56 67.97 37.66 104.22 51.42 48.25 33.70 75.53 191.23 44.31 85.95 121.36 1.75 48.73 70.15100 0.1 1 50 5 10 50 50mg mg/mL mg/mL mg/mL μg/inhalation mg mg mg/g0.25mg/mL(i.v.)7 16.7 7 2.5 40.59 10 153 1.1 1.1 1.089 0.008 0.04 0.07 0.1 0.003 0.08 0.2?2.79 ?1.77 0.05 ?2.24 ?2.24 ?2.34?0.70 ?0.40 ?0.40 1.31?1.14 ?0.40 ?0.15 1.31(i.v.)2.18 1.336.82 2.09 1.08(s.c.) (epidural) (i.v.) (s.c.) 0.08 2.4 3.134 0.1 0.2 0.10 0.2 0.08 0.1 (epidural) 0.5 0.0003 (i.v.) 120 100 0.17 1.65 3.58 8 0.3 0.2 0.64 200 16 0.041 250 4 2.5 3.9 2?2.34 ?0.08 ?1.31 ?3.84 ?0.68 ?3.23 ?2.08 ?1.82 ?1.62 0.5 0.5 8 30 6 0.5 1 3 8 ?3.60 ?2.19 ?1.951.84 3.21 ?2.74 2.441.16 2.66 ?2.39 1.88 1.80 2.39 4.85 4.85 2.39 2.84 1.43?3.70 ?3.79 ?0.67 ?0.83 ?0.88 ?2.15 ?3.33 ?8.48 ?1.35 ?2.14 ?4.71 ?5.36 ?1.62 ?3.53 1.48 ?2.09 ?3.422.96 2.73 ?0.67 ?0.66 ?0.66 0.22 3.97 5.39 2.93 2.50 1.24 ?0.99 1.84 3.69 ?2.82 1.95 0.170.1 0.1 3.22 2.4 3.412 13 5?3.37 ?3.48 ?1.89 ?2.01 ?1.81 24 0.5 ?0.41 ?0.422.72 1.95 0.70 3.93?0.11 1.44 1.75 0.70 2.07 2.30 1.80 0. 0.4 0. 4.9 10 10 ?3.06 0.57 ?1.23 1.88 ?0.02 ?0.28 2.18 0.16 0.14I amrinone lactate Indapamide Irinotecan Isoniazid Isosorbide 2-mononitrate Isosorbide 5-mononitrate Isosorbide dinitrate Ivabradine Ivermectin Ketamine Labetalol Letrozole Leuprolide Levamisole Levobupivacaine Levodopa Lidocaine Linezolid Liraglutide Lorazepam Lorcainide hydrochloride Maprotiline Maraviroc Melatonin Melphalan M pethidine Mepivacaine Meprobamate Mesna Methadone Methohexital Methylergonovine Methylphenidate Methylprednisolone Metoprolol Metronidazole Tablets Solution Tablets Tablets Tablets Tablets Tablets Tablets Solution Tablets Tablets Solution Tablets Solution Tablets Solution Tablets Solution Tablets Tablets Tablets Tablets Tablets Tablets Tablets Solution Tablets Tablets Tablets Solution Tablets Tablets Tablets Tablets Tablets Oral Injection Oral Oral Oral Oral Oral Oral Injection Oral Oral Injection Oral Injection Oral Injection Oral Injection Oral Oral Oral Oral Oral Oral Oral Injection Oral Oral Oral Injection Oral Oral Oral Oral Oral 365.84 586.69 137.14 191.14 191.14 236.14 468.60 875.12 237.73 328.41 285.31 .30 288.44 197.19 234.34 337.35 .17 370.93 277.41 513.68 232.28 305.21 247.34 246.36 218.25 142.20 309.46 262.31 339.44 233.31 374.48 267.37 171.162.5 20 300 10 20 40 7.5 3 100 300 2.5 45 50 7.5 250 20 600 6 2 100 75 300 5 2 100 20 400 400 10 10 0.2 20 32 100 500mg mg/mL mg mg mg mg mg mg mg/mL mg mg mg/mL mg mg/mL mg mg/mL mg mg/mL mg mg mg mg mg mg mg mg/mL mg mg mg mg/mL mg mg mg mg mg?3.96 ?2.88 ?1.17 ?3.53 ?2.78 ?0.39 ?1.65 ?2.74 ?1.53 1.69 ?2.46 ?3.13 ?3.30 ?1.75 ?3.87 ?0.81 ?1.432.37 4.48 4.52 3.26 1.03 ?0.21 2.23 2.10 0.92 ?1.55 4.17 1.81 1.76 2.56 1.74 1.49 ?0.464 6 3 6 6 8 6 13 2 4 4 16 2 2 5 2 5 59 3 2 1 4 2 4 2 2 2 3 2 3 3 2 5 4 42 1 2 1 1 0 0 3 1 4 0 16 0 1 4 1 1 54 2 0 1 1 2 2 0 1 2 2 0 1 3 1 3 2 1102.49 108.44 74.33 96.60 96.60 130.49 57.04 173.88 32.84 106.25 61.36 464.21 10.79 33.72 114.54 33.72 70.45 .71 20.32 14.57 57.98 55.92 69.67 28.24 33.72 110.07 59.79 19.45 70.56 70.55 41.64 104.22 55.03 77.52Benet, Broccatelli and Oprea3.4 10.3 50 2.2 0.5 0.008 0.02 0.4 2.91 ?0.75 ?3.12 ?1.00 ?0.44 0.89 1.03 2.09 1.92 3.00 0.36 ?2.87 3.82 1.17 ?2.45 ?4.47 ?4.27 ?5.19 1.62 2.97 4.04 0.72 0.43 1.62 2.97 3.60 3.60 1.69 ?0.53 ?0.87 ?0.87 0.91 ?1.78 ?1.70 ?1.13 1.28 0.90 ?1.55 ?0.96 ?1.98 ?2.72 3.27 0.05 1.24 1.53 0.04 1.380.07?1.892.15 4.242.15 2.52BDDCS Applied to Over 900 Drugs57.14 1 35.5 124 100 34 16.66
4.2 0 0.5 16.7 0.004 0.004 0.2 0.003 0.02 0.02Mexiletine Mianserin Micafungin sodium Midazolam hydrochloride Minocycline hydrochloride Minoxidil Mirtazapine Misoprostol Molindone Morphine hydrochloride Nafarelin Nalbuphine hydrochloride Nalmefene hydrochloride Naloxone Naltrexone Nefopam N nicotinic acid N nicotinamide Nicardipine Nicorandil Nicotine 0.002 0.0008 Sublingual Oral Oral Oral 0.8 0.01 0.02 0.002 0.002 0.1 0.05 1.0250 60 10 2 100 10 45 0.2 50 30 0.2 20 1 2 100 30
20 4mg mg mg/mL mg/mL mg mg mg mg mg mg mg/actuation mg/mL mg/mL mg mg mg mg mg mg mg mgOral Oral Injection (i.v.) Oral Oral Oral Oral Oral Oral Oral Topical (nasal) Injection (i.v.) Injection (i.v.) Oral Oral Oral Oral Oral Oral Oral Oral9.5 5 1 5.6 11 10 2 0.5 2 4 3 4 9.6 0 1 3179.26 264.37 .78 457.49 209.25 265.36 382.55 276.38 285.35 .45 339.44 327.38 341.41 253.35 123.11 122.13 479.54 211.18 162.24?0.12 ?2.73 ?7.93 ?3.92 2.53 ?1.86 ?2.31 ?5.01 ?1.77 ?1.26 ?5.45 ?2.41 ?2.87 ?2.14 ?2.10 ?2.39 ?0.05 ?1.01 ?4.96 ?1.98 ?0.25 2.57 3.76 ?2.59 3.42 0.19 ?0.72 2.81 3.07 2.57 0.57 ?1.22 1.39 2.64 0.16 0.36 2.91 0.80 0.80 5.23 0.75 0.88 2 2 22 2 9 5 3 4 3 4 17 5 4 5 5 2 3 2 6 5 2 1 0 16 0 5 2 0 2 1 2 17 3 2 2 2 0 1 1 1 1 0 37.08 2.05 554.51 20.12 175.38 89.15 12.29 90.45 42.21 55.71 510.46 78.27 55.71 73.98 73.98 9.97 51.07 56.49 114.03 99.54 11.420.4 0.35 0.25 0.5Capsules Tablets Solution Syrup Capsules Tablets Tablets Tablets Tablets Capsules Solution Solution Solution Tablets Tablets Tablets Capsules Tablets Capsules Tablets Tablets (as chewing gum) Tablets Tablets Tablets Tablets2 0.5 5.7 100.08 0.3 0.006 0.042.23 3.770.5 2 0 0 3 2 32 0 0 5 8 2 ?2.45 ?2.84 ?1.71 ?1.432.23 2.12 2.782.10 0.21 0.90 0.890.18 1.65 0.9875 1 40 40 8 100 75 5 80 15 80 40 .86 0.8 100 24 142.85 0.01 0.08 0.003 0.007 0.03 3 0.5 19 1.9 2mg mg mg mg Active metabolite mg mg/mL mg mg mg mg mg mg/mL mg mg mg mg mg Capsules Solution Tablets Tablets Tablets Tablets Capsules Solution Tablets Tablets Tablets Tablets Tablets Oral Injection (i.v.) Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Oral ?1.82 ?0.93 ?2.69 ?0.50 ?1.10 ?0.03227.09 298.43 369.51 312.46 259.35 263.39 .60 345.42 293.37 269.39 312.41 395.29 265.36 357.50 315.37 301.35 153.14?2.68 ?3.97 ?5.17 ?4.38 ?2.48 ?1.22 ?4.53 ?3.53 ?3.69 ?3.18 ?2.18 ?2.36 3.13 ?0.80 ?4.23 ?1.64 ?1.39 ?0.321.76 2.78 5.06 3.31 3.16 4.32 2.51 2.91 2.57 2.72 3.90 2.13 0.78 2.09 4.87 ?0.04 ?0.48 1.069 2 3 2 2 1 12 8 5 2 2 4 2 4 3 5 5 40 1 1 1 1 1 13 2 1 0 0 2 2 2 1 1 2 3169.35 40.83 62.44 40.83 41.64 14.57 367.50 150.96 71.04 29.66 9.97 96.67 48.49 55.34 50.80 60.22 73.98 91.375.4 11.4 100 191 1 0.70.03 0.1 0.01 0.008 0.2 0.60.27 0.29 ?2.37 ?2.64 1.47 3.16 ?0.31Nitroglycerin Norethindrone Norgestimate Norgestrel Nortilidine Nortriptyline Octreotide acetate Olmesartan medoxomil Omeprazole Ondansetron Orphenadrine Oseltamivir phosphate Oxaliplatin Oxprenolol Oxybutynin hydrochloride Oxycodone Oxymorphone p-Aminosalicylic acid (PAS) Pantoprazole sodium Paroxetine Pe?oxacin Pentamidine Pentoxifylline Perindopril erbumine Phenobarbital Phenylbutazone Phenylephrine hydrochloride Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Injection (i.v.) 0.008 1.4 0.38 0.1 9.09 333.33 50 1.0 0.01 0.05 0.4 0.04 0.001 0.001 0 2 12 12 0 8 24 1 383.38 329.37 333.37 340.43 278.31 368.48 232.24 308.38 167.21 ?1.79 ?1.47 ?0.53 ?0.16 ?4.7640 40 400 300 400 8 60 100 1mg mg mg mg mg mg mg mg mg/mL1.19 0.15 ?1.01 0.29 ?0.06 1.34 0.73 ?1.89 6.30 4.09?3.45 ?1.97 ?0.61 2.44 ?2.98 ?0.95 ?2.62 ?3.67 0.512.11 4.24 ?0.32 2.31 0.12 1.21 1.37 3.39 ?0.09 6.406 4 6 6 4 5 3 2 21 1 1 4 0 2 2 0 080.15 41.89 61.72 120.17 66.77 101.91 83.96 41.56 60.00Pimozide Pramlintide acetate Prazosin Prednisolone Primaquine Prochlorperazine Proguanil Promazine Promethazine Propantheline bromide2 0.6 5 5 15 10 100 100 50 15mg mg/mL mg mg mg mg mg mg mg mgTablets Tablets Tablets Powder Tablets Tablets Tablets Tablets Solution (with promethazine HCl) Tablets Solution Tablets Tablets Tablets Tablets Tablets Tablets Tablets Tablets Oral Injection (s.c.) Oral Oral Oral Oral Oral Oral Oral Oral0.5 16 1 0.1 2 2 3.5?2.44 ?2.98 ?3.57 ?1.45 0.07 ?0.87461.56 .41 360.45 259.35 373.95 253.74 284.43 284.43 368.501.62 4.88 2.53 4.55 4.81 ?1.070.79 1.62 ?0.07 2.98 2.52 2.64 ?1.07?5.02 ?17.83 ?3.62 ?3.68 0.32 ?4.05 0.28 ?2.04 ?2.21 ?4.172.03 1.42 2.60 4.38 2.53 4.40 4.40 1.492 60 7 5 4 3 5 2 2 11 56 1 3 2 0 5 0 0 033.99 .10 104.22 61.59 2.92 89.44 1.75 1.75 36.48527528Table I. (Continued)Generic name Formulation MW drug Route CLogPMaximum Maximum strength strength dose value dose unit Measured solubility (mg/mL) Dose number Measured LogS molar HBA Measured LogP Measured LogD74 % Excreted unchanged in urine minVSLgS 3C7.5HBDPSA0.253.4880 50 10 500 300 100 300 1 1.6 0.5 ?0.60 18 12 324.43 ?0.69 3.44 1.82 3.44 1.91 1.82 Capsules Oral 111.1 0.009 ?2.85 2.79mg mg mg mg mg mg mgTablets Tablets Tablets Tablets Tablets Tablets TabletsOral Oral Oral Oral Oral Oral Oral50 1.2 50 15 94 28.57 11.10.006 0.2 0. 0.01 0.01 0.1259.35 170.23 263.39 123.12 383.52 399.97 324.43?0.71 ?2.15 ?0.72 ?0.91 ?0.97 ?1.15 ?1.85 1.20 1.09 1.36 ?0.59 2.75 0.97 4.87 ?0.68 2.99 6.72 2.79?1.11 ?1.83 ?1.10 ?0.57 ?3.69 ?2.09 ?2.673 1 1 3 5 4 4 42 2 1 1 1 1 1 146.24 46.21 14.57 66.73 43.01 34.79 43.08 43.08260mg1.76 ?1.59 ?4.78 ?0.24 ?4.26 1.85 3.72 ?1.85 1.25 4.14 ?2.438 0.01 142 0.02 50 0.25 0.2 0.8 0.01 2 15 6 0.008 0.06 0.1 0.006 1.00.0030 0.1 1.5 10 0.1 1 17?0.55 ?3.223.040.08 2.52Propranolol hydrochloride Propylthiouracil Protriptyline Pyrazinamide Quetiapine fumarate Q mepacrine Quinidine sulfate dihydrate Quinine bisulfate heptahydrate Rabeprazole sodium Ramelteon Ramipril Reboxetine Remifentanil hydrochloride Reserpine Ribavirin Ridogrel Riluzole Rimantadine hydrochloride Risperidone Rivastigmine Rizatriptan Ropinirole Ropivacaine Rosiglitazone maleate Rotigotine Capsules Tablets Capsules Tablets Solution Tablets Tablets Tablets Tablets Tablets Tablets Capsules Tablets Tablets Solution Tablets Transdermal 42 133 53.8 0.04 5.6 2 20 3 0.1 14 5 1 0 0 2.70 2.90 4.03 ?0.81 ?0.29 ?0.71 ?3.95 ?1.75 Tablets Tablets Tablets Tablets 2.51 666.67 1.1 0.5 0. 384.90 138.12 303.36 238.29 359.45 259.35 416.52 313.40 376.46 608.69 244.21 366.34 234.20 179.31 410.50 250.34 269.35 260.38 274.41 357.43 315.48 1.15 3.40 ?3.73 ?3.49 ?1.27 ?2.11 ?3.15 ?5.80 ?0.90 ?3.58 ?2.72 1.85 ?3.49 ?1.56 ?1.19 ?0.33 ?3.25 ?3.80 ?2.44 2.08 2.49 1.54 3.26 1.96 3.86 ?2.85 4.54 3.24 3.96 2.71 2.10 0.99 2.80 3.16 3.02 4.54 Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Oral Oral Oral Oral Oral Injection (epidural) Oral Topical (skin. membranes) Oral Oral Oral Oral ?1.74 0.34 ?2.34 2.26 0.98 1.97 2.90 0.1 0.02 0.1 0.7 21.4 25 0.5 0.604 0.02 0.008 0.2 0.2 ?1.91 ?1.98 ?2.13 3.8 2.9 3.5 1.1 ?2.55 ?1.14 ?1.20 ?2.87 ?2.70 2.19 3.95 0.93 2.71 3.24 ?1.17 5.40 0.46 6.56 1.79 1.49 ?0.55 ?1.51 0.62 1.97 2.67 2.74 ?2.62 0.20 ?1.72 ?2.94 2.80 2.19 0.29 2.1620 8 10 6 1 0.25 200 5 50 100 4 6 10 5 10 8 18mg mg mg mg mg/mL mg mg mg mg mg mg mg mg mg mg/mL mg mg5 2 5 4 4 8 7 5 3 1 4 2 3 2 2 5 2 4 3 4 31 1 2 1 0 1 4 1 1 1 0 0 1 1 1 1 1 1 2 1 270.73 41.95 101.91 41.58 74.45 114.49 146.67 72.68 47.02 27.97 53.60 29.73 39.11 33.72 33.72 71.34 24.05 70.19 63.70 59.59 83.96150 300 10 100mg mg mg mgRoxatidine acetate HCl Salicylic acid Scopolamine Secobarbital (quinalbarbitone) S (?)-deprenil Sertraline hydrochloride Sibutramine Sildena?l Solifenacin succinate Spar?oxacin Sufentanil Sumatriptan succinate Sunitinib malate Tacrine Tamoxifen Tamsulosin Temazepam Temocapril Temsirolimus Tenoxicam Terazosin Theophylline Thioguanine Thiopental Tablets Tablets Capsules Tablets Tablets Tablets Solution Tablets Capsules Capsules Tablets Capsules Capsules Tablets Solution Tablets Tablets Tablets Tablets Powder 0.01 0.803 24.2 8.3 0.2 50 Oral Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Injection (i.v.) 0.10 0.002 0.3 0.8 0.085 100 15 100 10 200 0.05 100 50 40 20 0.4 30 4 10 20 10 600 40 1000mg mg mg mg mg mg mg/mL mg mg mg mg mg mg mg mg/mL mg mg mg mg mg0.1 0.2 0 7.5 12.5 10 6 22 4 0.5 0.5 8.7 0.5 1.5 4.6 0.1 10 18 0.5 0.5187.29 306.24 279.86 474.59 362.48 392.41 386.56 295.41 398.48 198.27 371.53 408.52 300.75 476.62 .38 387.44 180.17 167.19 242.34?0.04 2.85?0.32 ?4.64 ?0.02 2.84Benet, Broccatelli and Oprea?5.01 ?2.62 ?1.20 ?1.34 ?2.92 ?0.69?2.32 ?2.99 ?2.19 ?4.17 ?3.16 ?0.67 ?3.23 ?0.96 ?2.58 ?0.12 ?4.42 ?2.96 ?3.58 ?1.98 ?9.52 ?0.17 ?3.71 ?1.87 ?0.79 ?3.263.02 5.35 5.59 1.98 4.68 ?0.61 3.59 0.74 3.00 3.27 6.82 2.17 2.34 2.10 0.67 1.61 2.18 ?0.03 ?1.70 2.981 1 1 7 2 7 3 3 3 2 2 6 3 5 14 5 8 3 3 20 1 0 1 0 3 0 2 3 1 0 2 1 2 4 2 1 1 3 21.18 14.57 1.18 105.18 29.42 102.79 29.11 67.24 80.53 37.91 10.28 107.38 51.32 101.91 253.80 104.05 95.48 61.90 76.09 65.6910.8?2.57 5.90 3.55 3.37 1.91 ?0.332.74 20 12 0.38 2.63 1.16 2.53 2.42 5.03 4.82 1.63 1.60 0.65 2.02 0.69 1.16 2.30 1.63 3.140.03 0.1 0.0.5 0.1 15 22.5 1 0.1 20 ?2.06 ?1.09 ?1.43 ?3.03 1.83 ?0.35 1 1 2BDDCS Applied to Over 900 Drugs0. 0.1 0.04 0. 0.02 0.002 20 8 15 0.5 1.8 4 5 2.75 ?2.05 0.13 0.02 0.03 0.8 0.7Thioridazine Ticlopidine T tilidate Timolol Tinidazole Tolterodine Toremifene Tramadol Tranylcypromine sulfate Triamcinolone Triamcinolone acetonide Triazolam Tri?uoperazine Trihexyphenidyl (benzhexol) Trimetrexate glucuronate Tropisetron Urapidil Valacyclovir V valcyte Valproic acid Vardena?l Vasopressin 48 0.08 0.114 0.045 50 10 50 11 19 174 70 1.3 0.11 0.1 0.001 0.64 ?0.44 ?3.69 ?3.58 ?3.88 ?0.91 ?1.48 ?0.87 ?1.41 ?1.31 ?0.27 ?0.70 ?2.05 ?3.65 ?4.04200 250 50 20 500 2 60 50 10 4 4 0.5 10 5 200 5 5
20 60.8mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg/mL mg mg mg mg μg/mLOral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Injection (i.v.) Oral Injection (i.v.) Oral Oral Oral Oral Injection (s.c.)370.58 263.79 273.38 316.43 247.27 325.50 405.97 263.38 133.19 394.44 434.51 343.22 407.50 301.48 369.43 284.36 387.49 324.34 354.37 144.22 488.61 1084.25?3.53 ?3.48 ?2.77 ?0.74 ?1.71 ?2.28 ?4.75 ?0.59 ?0.33 ?3.07 ?4.17 ?4.21 ?3.80 ?1.94 ?3.54 ?1.94 ?3.74 ?1.59 ?1.54 ?1.45 ?4.03 ?2.25 6.00 4.39 3.76 1.21 ?0.32 5.24 6.53 3.10 1.48 0.71 2.21 2.62 4.69 5.15 1.84 2.88 2.44 ?1.22 ?2.18 2.76 2.23 ?3.82 2 1 2 7 5 2 2 3 1 6 6 3 3 2 8 2 6 7 9 2 7 16 0 0 0 2 0 1 0 1 1 4 2 0 0 1 3 1 1 3 4 1 1 15 1.75 1.18 28.24 75.98 91.72 24.05 10.28 32.84 27.97 126.78 99.25 33.27 2.92 23.73 117.41 42.21 63.11 144.80 167.36 40.83 104.88 504.484.6 1.5 0.5 15 113.79 3.703.69 2.57 ?0.77572 0.75 10 10 .1 0. 0.05 0.001 0.002 0.5 0.3 8 2.8 8 0.5 22 4.5 25 20 23 0.8 0.120.31 ?3.05 ?1.91 ?1.92 0.11 0.12 ?3.59Venlafaxine hydrochloride Verapamil hydrochloride Vinblastine Vincristine Vinorelbine tartrate Vitamin B6 (pyridoxine) Vitamin D3 (cholecalciferol) Vorozole Zidovudine Zolmitriptan Zolpidem tartrate Zonisamide Zopiclone ?1.03 ?1.16 ?1.13 ?2.42 ?3.51150 120 1 1 10 25 1.4 2.5 300 5 10 100 7.5mg mg mg/mL mg/mL mg/mL mg mg mg mg mg mg mg mgTablets Tablets Capsules Tablets Tablets Tablets Tablets Tablets Tablets Tablets Tablets Tablets Tablets Tablets Powder Capsules Solution Caplets Tablets Tablets Tablets Solution (20 units per mL) Tablets Tablets Solution Solution Solution Capsules Tablets Tablets Capsules Tablets Tablets Capsules Tablets Oral Oral Injection (i.v.) Injection (i.v.) Injection (i.v.) Oral Oral Oral Oral Oral Oral Oral Oral 277.41 454.61 811.00 824.98 778.95 169.18 384.65 324.78 267.25 287.36 307.40 212.23 388.82 0.05 0.08 1.50 2.35 ?0.10 ?0.90 ?1.52 ?4.11 ?6.97 ?6.35 ?6.71 ?0.75 ?6.71 ?4.16 ?2.31 ?1.03 ?4.20 ?1.30 ?2.84 3.27 4.47 5.23 4.04 5.94 ?0.35 9.48 2.20 0.04 1.29 3.03 ?0.36 1.25 3 6 9 9 8 4 1 4 6 2 3 3 6 1 0 3 3 2 3 1 0 2 2 0 1 0 32.84 56.29 152.61 170.88 130.05 78.23 22.56 50.83 127.30 56.78 29.96 88.84 79.29529530Table II. Measured and In Silico Data for 265 BDDCS Class 2 DrugsGeneric name Formulation MW drug 254.29 216.24 326.44 412.53 2.85 ?2.38 ?0.55 2.73 7.80 1.41 2.54 ?0.55 6.40 7.88 ?5.07 ?5.78 6.07 9.15 ?3.75 1.26 ?0.30 1.21 2.51 ?3.15 ?2.29 2 3 3 3 CLogP HBA 0.045 27 1 0 RouteMaximum strength dose value Measured solubility (mg/mL) Dose number Measured LogS molar minVSLgS 3C7.5 Measured LogP Measured LogD74 % Excreted unchanged in urine 2 1 1 1Maximum strength dose unitHBDPSA 32.78 49.94 49.94 49.9410-Hydroxy-carbamazepine 6-Methoxy-2-naphthyl-acetic acid Acitretin Adapalene Capsules Cream, gel, solution Tablets 0.569 2.1 0 1 12 0.5 Oral Topical (skin. membranes) OralActive metabolite Active metabolite25 6mg mg2002.3 5.00.7 0.1 0.04 0.05?2.96 ?3.97 ?4.10 ?4.360.000112000 3.5 1 0.5 0 16 0.5 8 ?6.65 3.20 5.70 ?7.44 ?3.27 3.00 1.96 3.00 ?0.17 3.880..156860.5 7 1 2 8 0.01 40Albendazole Albendazole sulfoxide Allopurinol Altretamine Aminoglutethimide Amiodarone hydrochloride Amphotericin B Amprenavir Anidulafungin Aprepitant Argatroban Aripiprazole Armoda?nil Artemether Astemizole Atazanavir sulfate Atorvastatin calcium Azelastine hydrochloride Bevantolol Bexarotene Beza?brate Bicalutamide Bosentan Buspirone Cabergoline C calcipotriol Tablets Capsules Tablets Tablets Solution Capsules Solution Capsules Solution Tablets Tablets Tablets Tablets Capsules Tablets Solution Tablets Capsules Capsules Tablets Tablets Tablets Tablets Solution 0.005 0.001 0..1 3 0.5 40 500 1.9 ?4.93 ?5.74 ?4.26 2.63 3.39 Capsules Cream Tablets 0.06 0.256 0.1 12 4.7 8 0 0.5 0.5 1 5 0 2 0.5 0 0.1 10 10 2.7 160 8.0 3.2 133 3.6 30 5.2 0.001 0. 0..9 13 34 416.65 305.42 236.28 252.28 Oral Oral Oral Oral Injection (i.v.) Oral Injection (i.v.) Oral Injection (i.v.) Oral Oral Oral Oral Oral Oral Ophthalmic Oral Oral Oral Oral Oral Oral Oral Topical (skin, membranes) Oral Topical Oral ?3.71 ?2.97 ?3.40 ?4.61 ?3.89 ?3.27 ?4.88 ?2.83 ?6.43 ?5.09 ?3.55 ?5.24 ?4.02 0.01 0.08 0.3 0.005 0.25 0. 0.1 0. 12 18 0.2 11 5 0.5 ?5.68 2.45 0.69 4.19 2.45 0.69 ?6.35 ?4.49 ?3.32 ?3.00300 50 250 400 2 50 3.33 125 1 30 250 50 10 300 80 457 200 75 200 50 125 10 0.5 0.05mg Active metabolite mg mg mg mg mg/mL mg mg/mL mg mg/mL mg mg mg mg mg mg μg/mL mg mg mg mg mg mg mg μg/mL265.34 281.34 136.11 210.28 232.28 645.32 924.10 505.64 .44 508.64 448.40 273.36 298.38 458.58 704.87 558.66 381.91 345.44 348.49 361.83 430.38 551.63 385.51 451.62 412.62?3.54 ?3.28 ?1.18 ?3.02 ?2.35 ?5.40 ?6.40 ?5.03 ?10.68 ?5.28 ?1.80 ?4.64 ?2.82 ?3.35 ?5.40 ?7.38 ?6.47 ?2.37 ?3.15 ?4.74 ?3.79 ?4.32 ?5.38 ?3.50 ?4.28 ?5.583.46 3.46 0.63 1.67 0.77 8.95 ?3.65 3.29 2.20 4.60 ?0.57 5.31 0.94 3.05 6.09 5.92 4.46 4.01 3.00 8.19 3.70 2.71 4.17 2.19 4.77 5.27 6.04 4.00 2.38 0.243 3 3 6 3 3 17 6 17 5 9 4 2 5 4 7 5 3 5 2 4 5 9 6 4 3 3 3 1 12 2 2 0 2 0 12 3 14 2 6 1 1 0 1 5 4 0 2 1 2 2 2 0 2 3 3 2 1 165.55 65.55 70.47 33.35 78.79 37.97 347.83 139.36 415.56 78.12 192.20 43.70 64.62 49.50 35.37 186.22 119.06 33.17 64.45 40.83 82.78 110.56 142.96 60.25 118.24 67.68 67.68 64.82 46.81 55.610.5 179 300μg mg mg Active metaboliteCalcitriol Capsaicin Carbamazepine Carbamazepine 10,11-epoxide Carvedilol Cefditoren pivoxil Cefpodoxime proxetil Celecoxib Chlorzoxazone Ciclesonide Cilostazol Cinacalcet Cisapride Citalopram Cladribine Clofazimine Clo?brate Clopidogrel bisulfate Clotrimazole Clozapine Tablets Tablets Tablets Capsules Tablets Solution Tablets Tablets Tablets Tablets Solution Capsules Capsules Tablets Tablets Tablets Oral Oral Oral Oral Oral Topical (nasal) Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Oral25 200 200 200 500 0.16 100 90 20 40 1 50 500 75 10 100mg mg mg mg mg mg/inhalation mg mg mg mg mg/mL mg mg mg mg mg406.49 620.73 557.61 381.38 169.57 540.70 369.47 357.42 465.96 324.40 285.69 473.41 242.70 321.83 344.85 326.833.41 0.02 7.48 3.60 4.80 3.233.39 0.74 0.24 3.60Benet, Broccatelli and Oprea?3.80 ?5.06 ?4.442.99?4.30 ?6.88 ?4.79 ?4.47 ?1.77 ?6.25 ?4.87 ?3.12 ?4.57 ?2.83 ?2.15 ?5.84 ?1.63 ?3.83 ?5.07 ?4.374.04 2.71 0.80 4.37 2.51 5.25 3.53 6.35 3.81 3.13 ?0.91 7.70 3.02 4.21 5.25 3.715 9 10 3 2 6 5 1 6 3 7 4 3 2 1 43 2 2 1 1 1 1 1 2 0 3 1 1 0 0 178.42 176.19 183.53 78.91 42.53 103.75 81.66 14.57 88.69 28.67 112.88 34.09 36.17 28.24 10.81 25.631 0.1 1 2.95 2.92 0.97 0.970.15 0.008 0.9 0.2 0.15 50 95 889 2.0 16 1.83 1.83 0.81 0..15 0.128 988 260 2.7 3.1 1.81 2.07 4.44 1.96 3.88 3.90 6.97 ?3.05 3.78 3.33 3.71 3.88 1.08 1.86 0.76 ?4.13 ?5.75 ?6.61 ?3.19 ?3.42?3.55 ?5.18 ?5.30 ?5.57 ?3.09 ?3.56BDDCS Applied to Over 900 Drugs5 100 50 200 100 600 70 5 200 5 100 100 500 500 75 250 40 20 10 10 0.007 0.2 0. 0. 43 5.0 15 1.2 0.1 0.5 2.5 5 35 0.5 6 1 0.1 0 5 0 10.6 0.5 ?4.86 ?3.17 ?5.09 ?4.85 ?5.12 0.5 3.2mg/ml mg mg mg mg mg mg mg/mL mg mg mg mg mg mg mg mg mg/mL mg mg mgSolution Capsules Tablets Capsules Tablets Capsules Tablets Solution Caplets Tablets Capsules Tablets Tablets Tablets Tablets Tablets Solution Tablets Tablets CapsulesInjection (i.v.) Oral Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral Oral Oral Oral Oral Oral Injection (i.v.) Oral Oral Oral498.59 .95 337.47 248.31 547.68 488.02 527.53 456.57 310.83 230.67 336.30 250.20 328.15 504.64 296.54 807.90 425.92 379.50 314.47?6.73 ?10.73 ?4.83 ?4.54 ?2.71 ?5.44 ?4.70 ?3.89 ?4.80 ?2.42 ?2.00 ?3.06 ?2.17 ?4.03 ?4.21 ?4.19 ?7.05 ?4.31 ?4.10 ?5.91 5.00 14.36 3.96 3.93 0.89 2.89 2.88 0.84 2.41 3.83 1.42 3.66 4.40 3.09 1.49 3.88 4.08 4.27 4.60 7.24 3 12 3 2 4 7 8 11 6 2 3 4 3 2 12 0 10 3 4 2 2 5 0 1 2 3 3 5 3 1 1 2 2 0 4 0 5 2 0 1 75.90 290.07 63.61 45.90 92.10 148.15 101.85 200.34 110.60 24.82 61.41 101.12 63.70 55.94 134.70 2.35 240.13 66.80 37.66 31.982.78 ?4.80 ?4.26 0.85 ?2.99 ?5.29 2.06 3.81 3.05 1.14 3.050.005 0. 0. 5.3480 480.01 0.045 0.14 3.4240?4.46 ?3.73 ?3.413.86 5.25 5.78 4.16 3.35 ?0.52 2.32 4.85 1.36 1.91 1.33 ?0.07 4.80 2.06 4.90 3.48 0.91 4.060.013 0.001 0.5 0. 0.51 0. 0.022 0.001 0. 0.2 0.004 0.037 0.038 53 3.9 13 9.0 7.3 200 588 126 82 13 6.0 2.2 8425 40 725 15 2.4 1.30 0.1 0.5 2 0.5 0.2 3 0.3 4 0.05 0.3 1 2 0.5 0 1 2 3 0.25 0.1 7 0.2 0.1 2.9 0.5 3 ?4.39 ?5.58 ?5.65 ?4.03 ?4.39 ?4.22 ?4.46 ?5.99 ?5.44 ?3.28 ?4.41 ?5.78 ?5.42 ?4.12 ?4.92 ?5.61 ?5.09 ?4.01 ?3.73 2.18 4.30 3.97 0 0 0.1 2 0.5 0.5 0 4.5 0 0.3 1 0.5 0.5Conivaptan hydrochloride Cyclosporine Cyproterone acetate Danazol Dapsone Darunavir Dasatinib Daunorubicin Delavirdine Desloratadine Diazoxide Dicoumarol Di?unisal Diloxanide furoate Dipyridamole Disul?ram Docetaxel Domperidone Donepezil D tetrahydrocannabinol Dronedarone Drospirenone Dutasteride Ebastine Efavirenz Entacapone Eplerenone Erlotinib hydrochloride Estazolam Ethchlorvynol Etizolam E}