TY - JOUR T1 - Content and Activities of UGT2B7 in Human Liver In Vitro and Predicted In Vivo: A Bottom-Up Approach JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1351 LP - 1359 DO - 10.1124/dmd.118.082024 VL - 46 IS - 9 AU - Chen Xu AU - Jie Gao AU - Hai-Feng Zhang AU - Na Gao AU - Yuan-yuan Guo AU - Yan Fang AU - Qiang Wen AU - Hai-Ling Qiao Y1 - 2018/09/01 UR - http://dmd.aspetjournals.org/content/46/9/1351.abstract N2 - UDP-glucuronosyltransferase 2B7 (UGT2B7) is one of the most significant isoforms of UGTs in human liver. This research measured UGT2B7 protein content and activities, including maximum velocity (Vmax) and intrinsic clearance (CLint), in human liver at isoform, microsomal, liver tissue, and liver levels and identified the factors that influence expression. We determined absolute protein content by liquid chromatography–tandem mass spectroscopy and activities using the probe drug zidovudine in 82 normal human liver microsomes. Using a bottom-up method for derivation, we showed UGT2B7 content at the microsomal, liver tissue, and liver levels, as well as activities at the isoform, microsomal, liver tissue, and liver levels in vitro, and predicted hepatic clearance in vivo, with median, range, variation, and 95% and 50% prediction intervals. With regard to the intrinsic activities, the maximum velocity (Vmax) had a median (range) of 7.5 (2–24) pmol/min per picomole of 2B7, and the CLint was 0.08 (0.02–0.31) μl/min per picomole of 2B7. Determinations at liver level showed larger variations than at microsomal level, so it was more suitable for evaluating individual differences. By analyzing factors that affect UGT2B7, we found that: 1) The content at the liver tissue and liver levels correlated positively with activities; 2) the mutant heterozygotes of -327G>A, -900A>G, -161C>T may lead to decreased protein content and increased intrinsic CLint; and 3) the transcription factor pregnane X receptor mRNA expression level was positively associated with the measured protein content. In all, we showed that protein content and activities at different levels and the factors that influence content provide valuable information for UGT2B7 research and clinically individualized medication. ER -