Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China.
Curr Top Med Chem. 2013;13(11):1343-52. doi: 10.2174/15680266113139990038.
Glucuronidation has been recognized as an important clearance mechanism in humans. Therefore, knowledge about the contribution of glucuronidation to clearance of drug candidates is of great value in early drug development. In this article, we discuss the recent progress made to predict in vivo glucuronidation parameters (e.g., hepatic clearance, and intestinal availability) using in vitro data, which are readily obtained using microsomes and hepatocytes, so called "in vitro- in vivo extrapolation" (IVIVE). Of note the intrinsic clearances obtained from microsomal incubations in the presence of bovine serum albumin (BSA) provide accurate predictions of the in vivo clearances in addition to those from hepatocytes. Further, we describe the lack of correlation between cellular and microsomal production of glucuronide and provide possible reasons. Due to the high prediction accuracy, those who study in vitro glucuronidation are encouraged to map their data to in vivo using IVIVE strategy for more informative data interpretation.
葡糖醛酸化已被认为是人体内一种重要的清除机制。因此，了解葡糖醛酸化对候选药物清除率的贡献在药物早期开发中具有重要价值。本文讨论了利用体外数据（如肝清除率和肠可利用性）预测体内葡糖醛酸化参数的最新进展，这些数据可以使用微粒体和肝细胞很容易地获得，这被称为“体外-体内外推法（IVIVE）”。值得注意的是，在含有牛血清白蛋白（BSA）的微粒体孵育中获得的内在清除率除了来自肝细胞的清除率外，还能准确预测体内清除率。此外，我们还描述了细胞内和微粒体内生成的葡萄糖醛酸化物之间缺乏相关性，并提供了可能的原因。由于预测准确性高，鼓励研究体外葡糖醛酸化的人员使用 IVIVE 策略将其数据映射到体内，以便更有意义地解释数据。
