Contribution of Molecular Properties to Extrapolation of the Volume of Distribution in Human from Preclinical Animal Species Data
文献类型：期刊论文
| 作者 | Sui, Xiaofan1,2; Sun, Jin1; Li, Haiyan1,3 ; Pan, Yang2; Wang, Yongjun1; He, Zhonggui1
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| 刊名 | BIOPHARMACEUTICS & DRUG DISPOSITION
 |
| 出版日期 | 2010-11 |
| 卷号 | 31期号:8-9页码:464-475 |
| 关键词 | volume of distribution molecular descriptors partial least squares allometric method |
| ISSN号 | 0142-2782 |
| DOI | 10.1002/bdd.727 |
| 文献子类 | Article |
| 英文摘要 | This paper quantitatively investigated the contribution of molecular properties to the volume of distribution in human (V-d human) when extrapolated from preclinical animal data, and identified which molecular descriptors and animal species were essential or better for acquiring the optimal accuracy of extrapolation. First, several two-dimensional molecular descriptors which can potentially contribute to V-d were selected to establish the model to predict V-d in humans. Then, several linear predictive models were constructed by partial least squares (PLS) using three or one animal data in combination with or without the molecular descriptors. Stepwise regression was performed to determine the important molecular descriptors. For comparison, the allometric method was also performed to estimate the V-d human from preclinical species (rat, dog and monkey) data. The predictive accuracy of PLS models was better than that obtained by the allometric method. Moreover, the predictive accuracy of these models was improved when the molecular descriptors were introduced. Interestingly, the common contributors selected were molecular weight (MW) and the negatively charged fraction value (f(i-)) for any stepwise regression model concerning molecular descriptors. Additionally, the dog was a more suitable species for predicting V-d human during drug-lead pharmacokinetic optimization. More importantly, the introduction of molecular properties could improve the predictive accuracy for the prediction of V-d human from the preclinical species, among which MW and f(i-) were the significant parameters and the latter was considered in the extrapolation process for the first time. Copyright (C) 2010 John Wiley & Sons, Ltd. |
| WOS关键词 | INTRAVENOUS PHARMACOKINETIC PARAMETERS ; PREDICTION ; MONKEY ; RAT ; DOG |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000284716100004 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278734]  |
| 专题 | 药物制剂研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | He, Zhonggui |
| 作者单位 | 1.Shenyang Pharmaceut Univ, Sch Pharm, Dept Biopharmaceut, Shenyang 110016, Peoples R China; 2.Liaoning Prov Inst Control Food & Drug Prod, Shenyang 110023, Peoples R China; 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sui, Xiaofan,Sun, Jin,Li, Haiyan,et al. Contribution of Molecular Properties to Extrapolation of the Volume of Distribution in Human from Preclinical Animal Species Data[J]. BIOPHARMACEUTICS & DRUG DISPOSITION,2010,31(8-9):464-475. |
| APA | Sui, Xiaofan,Sun, Jin,Li, Haiyan,Pan, Yang,Wang, Yongjun,&He, Zhonggui.(2010).Contribution of Molecular Properties to Extrapolation of the Volume of Distribution in Human from Preclinical Animal Species Data.BIOPHARMACEUTICS & DRUG DISPOSITION,31(8-9),464-475. |
| MLA | Sui, Xiaofan,et al."Contribution of Molecular Properties to Extrapolation of the Volume of Distribution in Human from Preclinical Animal Species Data".BIOPHARMACEUTICS & DRUG DISPOSITION 31.8-9(2010):464-475. |
入库方式： OAI收割
来源：上海药物研究所
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