title: Corydaline inhibits multiple cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes.
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 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.
authors.affiliation: Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Ji
authors.forename: Kwang Hyeon
authors.initials: KH
authors.lastname: Liu
authors.forename: Hyeri
authors.initials: H
authors.lastname: Lee
authors.forename: Sae Rom
authors.initials: SR
authors.lastname: Im
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Shim
authors.forename: Miwon
authors.initials: M
authors.lastname: Son
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology; D018926:Anti-Allergic Agents / Q000737:chemistry* / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001600:Berberine Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D031311:Corydalis / Q000737:chemistry*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D053719:Tandem Mass Spectrometry
chemical_list: D000700:Analgesics; D018926:Anti-Allergic Agents; D001600:Berberine Alkaloids; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; C452799:corydaline; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase