Glucuronidation of buprenorphine and norbuprenorphine by human liver microsomes and UDP-glucuronosyltransferases.
We investigated the enzyme kinetics of buprenorphine and norbuprenorphine glucuronidation in human liver microsomes and UDP-glucuronosyltransferase (UGT) Supersomes. The involvement of UGT 1A1, 1A3 and 2B7 in buprenorpine and 1A3 in norbuprenorphine glucuronidation were confirmed. Novel involvement of 2B17 with buprenorphine and 1A1 with norbuprenorphine were demonstrated. Scaling of buprenorphine clearance with, or without, correction for the nonspecific microsomal protein binding of buprenorphine (f(u) = 0.42) suggested glucuronidation was a significant route for hepatic clearance of buprenorphine.
Chang
Yan
Y
Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84108, USA. changyan_wang@hotmail.com
Moody
David E
DE
D000701:Analgesics, Opioid / Q000378:metabolism; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D020719:Glucuronides / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D011485:Protein Binding
D000701:Analgesics, Opioid; D020719:Glucuronides; D002047:Buprenorphine; C043585:norbuprenorphine; D014453:Glucuronosyltransferase