Mechanism Analysis for the Influence of Propofol's Therapeutic Window by Purpurin
作者
Xing, CY;Wu, MY;Li, W;Zhou, XY;Zhang, MY
作者单位
[Xing, Cui-Yan; Li, Wei; Zhou, Xiao-Yang; Zhang, Meng-Yuan] Shandong Univ, Affiliated Prov Hosp, Dept Anesthesiol, Jinan 250021, Shandong, Peoples R China.;-;[Wu, Ming-Yi] Shandong Univ, Affiliated Prov Hosp, Pain Dept, Jinan 250021, Shandong, Peoples R China.
摘要
Drug-drug interaction (DDI) strongly limits the clinical application of propofol which has been clinically used as a short-acting, intravenously administered hypnotic agent. The present study aims to determine the inhibition of propofol glucuronidation by purpurin which is a natural anthraquinone pigment isolated from madder root (Rubia tinctorum L.). The results showed that purpurin exhibited concentration-dependent inhibition towards the glucuronidation of propofol, and noncompetitive inhibition behavior of purpurin towards propofol glucuronidation was demonstrated by inhibition kinetic study (Dixon plot). Given that UGT1A9 was the major drug-metabolizing enzyme involved in the metabolism of propofol, detailed mechanism was furtherly investigated through evaluating the inhibition of purpurin towards recombinant UGT1A9-catalyzed 4-methylumbelliferone. The concentration-dependent inhibition of purpurin towards the formation of 4-MU glucuronide was also detected, demonstrating the inhibition of purpurin towards the activity of UGT1A9. All these results showed that purpurin affected the therapeutic window of propofol thorough influence of the activity of UGT1A9, reminding the clinical importance to monitor the drug-drug interaction when co-administering propofol and purpurin.
关键词
HYPNOTIC AGENT PROPOFOL; STRONG INHIBITION; GLUCURONIDATION; METABOLISM
基本信息
