TY - JOUR
T1 - Quantitative prediction of glucuronidation in humans using the in vitro-in vivo extrapolation approach
AU - Wu, Baojian
AU - Dong, Dong
AU - Hu, Ming
AU - Zhang, Shuxing
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Drug metabolism
KW - Glucuronidation
KW - In vitro-in vitro correlation
KW - In vitro-in vitro extrapolation
KW - Quantitative prediction
KW - UGTs
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U2 - 10.2174/15680266113139990038
DO - 10.2174/15680266113139990038
M3 - Article
C2 - 23675940
AN - SCOPUS:84881324657
SN - 1568-0266
VL - 13
SP - 1343
EP - 1352
JO - Current Topics in Medicinal Chemistry
JF - Current Topics in Medicinal Chemistry
IS - 11
ER -