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Corydaline Inhibits Multiple Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes
Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea
Research Center, Dong-A Pharmaceutical Co., Yongin 446-905, Korea
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 22 June 2011; in revised form: 27 July 2011 / Accepted: 2 August 2011 / Published: 5 August 2011
Abstract: 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 Ki 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 Ki 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 Ki 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.
Keywords: corydaline; cytochrome P450 inhibition; UDP-glucuronosyltransferase inhibition; human liver microsomes; drug-drug interaction
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Ji, H.Y.; Liu, K.H.; Lee, H.; Im, S.R.; Shim, H.J.; Son, M.; Lee, H.S. Corydaline Inhibits Multiple Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes. Molecules 2011, 16, 6591-6602.
Ji HY, Liu KH, Lee H, Im SR, Shim HJ, Son M, Lee HS. Corydaline Inhibits Multiple Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes. Molecules. 2011; 16(8):6591-6602.
Ji, Hye Young; Liu, Kwang Hyeon; Lee, Hyeri; Im, Sae Rom; Shim, Hyun Joo; Son, Miwon; Lee, Hye Suk. 2011. "Corydaline Inhibits Multiple Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes." Molecules 16, no. 8: 6591-6602.