BDDCS Applied to Over 900 Drugs
BDDCS Applied to Over 900 Drugs
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DOI：
10.1208/s12248-011-9290-9
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发表时间：
2011-12-01
期刊：
影响因子：
4.5
通讯作者：
Oprea, Tudor I.
中科院分区：
文献类型：
--
作者：
Benet, Leslie Z.;Broccatelli, Fabio;Oprea, Tudor I.
在这里，我们编制了927种药物的生物制药药物处置分类系统(BDDCS)，其中包括30种活性代谢物。在897种母药中，78.8%(707)是口服的。如果发现测量到的最低溶解度，则报告这些口服药物中72.7%(513)的溶解度并记录剂量数字。测量值报告尿中排泄百分比、LogP和LogD(7.4)(如果有)。对于所有927个化合物，还提供了预测的对数在水中的溶解度的电子参数，计算的对数P，极性表面积，以及活性部分的氢键受体和氢键供体的数量，从而可以对电子和实验测量值进行比较分析。我们讨论了BDDCS在药物发现和开发的早期阶段评估新化学品(新分子实体)的处置特征的潜在用途。肠道和肝脏中的转运体效应与BDDCS 1类药物临床无关，但可能对2类(肠道内的外排，以及肝脏的外排和摄取)和3类(肠道和肝脏的摄取和外排)药物有很大的影响。高剂量和低溶解度的组合可能导致BDDCS第4类药物在已批准药物方面供不应求(N=53，而第1-3类药物各超过200)。详细讨论了BDDCS分类过程中几个测量参数和计算机参数的影响。
Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification 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 LogD (7.4) 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 (efflux in the gut, and efflux and uptake in the liver) and class 3 (uptake and efflux 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 1-3). The influence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail.