Predicting drug disposition via application of BCS: Transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system
Predicting drug disposition via application of BCS: Transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system
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DOI：
10.1007/s11095-004-9004-4
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发表时间：
2005-01-01
影响因子：
3.7
通讯作者：
Benet, LZ
中科院分区：
文献类型：
--
作者：
Wu, CY;Benet, LZ
开发了生物药剂学分类系统（BCS），以允许通过渗透性（确定为口服吸收程度）和溶解度的测量来预测制剂的体内药代动力学性能。在这里，我们建议这种分类系统的修改版本可能有助于预测总体药物处置，包括药物消除途径以及外排和吸收转运蛋白对口服药物吸收的影响;当转运蛋白-酶相互作用将产生临床显著影响时（例如，低生物利用度和药物-药物相互作用）;食物效应的方向、机制和重要性;以及转运蛋白对口服和静脉给药后吸收后全身药物浓度的影响。这些预测得到了我们实验室在过去几年中的一系列研究的支持，这些研究调查了转运蛋白抑制和诱导对药物代谢的影响。我们的结论是，建议生物药剂学药物处置分类系统（BDDCS）使用消除标准可能会扩大I类药物的数量有资格豁免的体内生物等效性研究，并提供药物处置概况的可预测性2类，3类和4类化合物。
The Biopharmaceutics Classification System (BCS) was developed to allow prediction of in vivo pharmacokinetic performance of drug products from measurements of permeability (determined as the extent of oral absorption) and solubility. Here, we suggest that a modified version of such a classification system may be useful in predicting overall drug disposition, including routes of drug elimination and the effects of efflux and absorptive transporters on oral drug absorption; when transporter-enzyme interplay will yield clinically significant effects (e.g., low bioavailability and drug-drug interactions); the direction, mechanism, and importance of food effects; and transporter effects on postabsorption systemic drug concentrations following oral and intravenous dosing. These predictions are supported by a series of studies from our laboratory during the past few years investigating the effect of transporter inhibition and induction on drug metabolism. We conclude by suggesting that a Biopharmaceutics Drug Disposition Classification System (BDDCS) using elimination criteria may expand the number of Class I drugs eligible for a waiver of in vivo bioequivalence studies and provide predictability of drug disposition profiles for Classes 2, 3, and 4 compounds.