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
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