Deep understanding of the interaction between thienorphine and UDP-glucuronosyltransferase (UGT) isoforms
1.Thienorphine has been demonstrated to be a potent,long-acting partial opioid agonist.It is being developed as a good candidate to treat opioid dependence.2.The thienorphine”s glucuronide was detected after thienorphine was incubated with human liver microsomes (HLMs).Recombinant UGT isoforms screening experiment and enzyme kinetic study showed that UGT1A1 completely contributed to the glucuronidation of thienorphine.3.Among the tested UGT isoforms,UGT1A3 and UGT2B7 were inhibited by thienorphine,with other UGT isoforms negligibly influenced.The inhibition type is competitive,and inhibition kinetic parameters (Ki) were 1.65 and 5.27 μM for UGT1A3 and UGT2B7,respectively.However,due to low plasma concentration of thienorphine,in vivo drug-drug interaction might not occur.
Thienorphine UDP-glucuronosyltransferase (UGT) drug-drug interaction
DONG Rui-hua GE Guang-bo ZHU Liang-liang GAO Xin WU Yuan YANG Ling LIU Ze-yuan
Department of Clinical Pharmacology, Affiliated Hospital, Academy of Military Medical Sciences.Beiji Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Acade
国内会议
成都
英文
137-143
2012-10-26（万方平台首次上网日期，不代表论文的发表时间）