Abstract:
: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.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Wu B,Dong D,Hu M,Zhang Sdoi
10.2174/15680266113139990038subject
Has Abstractpub_date
2013-01-01 00:00:00pages
1343-52issue
11eissn
1568-0266issn
1873-4294pii
CTMC-EPUB-20130509-8journal_volume
13pub_type
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