TY - JOUR T1 - 3′-azido-3′-deoxythimidine (AZT) is glucuronidated by human UDP-glucuronosyltransferase 2B7 (UGT2B7) JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 497 LP - 502 VL - 28 IS - 5 AU - Olivier Barbier AU - David Turgeon AU - Caroline Girard AU - Mitchell D. Green AU - Thomas R. Tephly AU - Dean W. Hum AU - Alain Bélanger Y1 - 2000/05/01 UR - http://dmd.aspetjournals.org/content/28/5/497.abstract N2 - 3′-Azido-3′-deoxythymidine (AZT) is frequently prescribed to patients infected with the human immunodeficiency virus. After absorption, AZT is rapidly metabolized into 3′-azido-3′-deoxy-5′-glucuronylthymidine by UDP-glucuronosyltransferase (UGT) enzymes. Using labeled [14C]UDP-glucuronic acid and microsomal preparations from human kidney 293 cells stably expressing the different human UGT2B isoenzymes, it was demonstrated that AZT glucuronidation is catalyzed specifically by human UGT2B7. The identity of the metabolite formed was confirmed as AZT-G by liquid chromatography coupled with mass spectrometry. UGT2B7 is encoded by a polymorphic gene and kinetic analysis of AZT glucuronidation by the two allelic variants UGT2B7(H268) and UGT2B7(Y268), yielded apparent Km values of 91.0 and 80.1 μM, respectively. Normalization to protein levels yielded glucuronidation efficiency ratios (Vmax/Km) of 21.3 and 11.0 μl · min−1 · mg protein−1for UGT2B7(H268) and UGT2B7(Y268), respectively. It remains possible that other UGT enzymes are also involved in AZT conjugation; however, the glucuronidation of AZT by UGT2B7, which is a UGT2B protein expressed in the liver, is consistent with previous findings and supports the physiological relevance of this enzyme in AZT conjugation. The American Society for Pharmacology and Experimental Therapeutics ER -