Quantitative Prediction of Glucuronidation in Humans Using the In Vitro- In Vivo Extrapolation Approach

Author(s): Baojian Wu, Dong Dong, Ming Hu, Shuxing Zhang.

Journal Name: Current Topics in Medicinal Chemistry

Volume 13 , Issue 11 , 2013

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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.

Keywords: Drug metabolism, glucuronidation, UGTs, in vitro-in vitro extrapolation, in vitro-in vitro correlation, quantitative prediction.

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Article Details

Year: 2013
Page: [1343 - 1352]
Pages: 10
DOI: 10.2174/15680266113139990038
Price: $58

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