Corydaline Inhibits Multiple Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

Molecules

Hye Young Ji¹  Kwang Hyeon Liu¹  Hyeri Lee¹  Sae Rom Im¹  Hyun Joo Shim¹  Miwon Son¹ 

[1] ¹Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea

关键词: corydaline;    cytochrome P450 inhibition;    UDP-glucuronosyltransferase inhibition;    human liver microsomes;    drug-drug interaction;   

DOI  :  10.3390/molecules16086591

来源: mdpi

【 摘 要 】

Corydaline is a bioactive alkaloid with various antiacetylcholinesterase, antiallergic, and antinociceptive activities found in the medicinal herb Corydalis Tubers. The inhibitory potential of corydaline on the activities of seven major human cytochrome P450 and four UDP-glucuronosyltransferase enzymes in human liver microsomes was investigated using LC-tandem MS. Corydaline was found to inhibit CYP2C19-catalyzed S-mephenytoin-4’-hydroxylatoin and CYP2C9-catalyzed diclofenac 4-hydroxylation, with K_i values of 1.7 and 7.0 mM, respectively. Corydaline also demonstrated moderate inhibition of UGT1A1-mediated 17b-estradiol 3-glucuronidation and UGT1A9-mediated propofol glucuronidation with K_i values of 57.6 and 37.3 mM, respectively. In the presence of corydaline, CYP3A-mediated midazolam hydroxylation showed a decrease with increasing preincubation time in a dose-dependent manner with K_i values of 30.0 mM. These in vitro results suggest that corydaline should be evaluated for potential pharmacokinetic drug interactions in vivo due to potent inhibition of CYP2C19 and CYP2C9.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.