Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide.

Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Research Abstract Details 

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Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Abstract Text:

H Xu,K M Williams,W S Liauw,M Murray,R O Day,A J McLachlan,

Background and purpose:Patients commonly take complementary medicines in conjunction with conventional drugs without clear evidence of safety or the risk of herb-drug interactions. The aim of this study was to assess potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between St John's wort and gliclazide in healthy subjects with different cytochrome P450 2C9 (CYP2C9) genotypes.Experimental approach:A crossover controlled study was conducted in 21 healthy subjects. Each received gliclazide (80 mg) either alone or during 15 days treatment with St John's wort. The area under the plasma concentration-time curve (AUC(0-infinity)), apparent clearance (CL/F) and elimination half-life (t (1/2)) of gliclazide and incremental changes in glucose and insulin AUC(0-4) were compared. CYP2C9*2 and CYP2C9*3 alleles were identified using PCR followed by restriction enzyme digestion analysis.Key results:St John's wort significantly altered gliclazide pharmacokinetics in all except for four healthy subjects. The mean ratio and 90% confidence interval (CI) of gliclazide AUC(0-infinity) and CL/F were 0.67 (0.55-0.81) and 1.50 (1.24-1.81), respectively, after St John's wort treatment. St John's wort decreased gliclazide t (1/2), with mean ratio and 90% CI of 0.85 (0.74-0.93). There were no significant changes in glucose or insulin AUC(0-4) after St John's wort treatment and no significant differences according to CYP2C9 genotype.Conclusions and implications:Treatment with St John's wort significantly increases the apparent clearance of gliclazide which is independent of CYP2C9 genotype. People with diabetes receiving this combination should be closely monitored to evaluate possible signs of reduced efficacy.British Journal of Pharmacology (2008) 153, 1579-1586; doi:10.1038/sj.bjp.0707685; published online 21 January 2008.

Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Publishing Authors By Initials

H Xu,KM Williams,WS Liauw,M Murray,RO Day,AJ McLachlan,

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Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: British journal of pharmacology

VOLUME: 153

Page Numbers: 1579-86

Journal Abbreviation: Br. J. Pharmacol.

ISSN: 0007-1188

DAY: 21

MONTH: 01

YEAR: 2008

Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Information

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LANGUAGE: eng

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AFFILIATION: 1Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.

Country: England

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MEDLINETA: Br J Pharmacol

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