Marine L Andersson1, Erik Eliasson, Jonatan D Lindh. 1. Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, SE 141 86, Stockholm, Sweden. marine.andersson@karolinska.se
Abstract
BACKGROUND: Simvastatin interacts with warfarin, but the strength of the interaction varies between individual patients, indicating a genetic predisposition. PATIENTS & METHODS: The influence of the CYP2C9*2 and CYP2C9*3 polymorphisms on the interaction between simvastatin and warfarin was analyzed in data from 1132 patients. RESULTS: Simvastatin use reduced warfarin dose requirements by 29% in carriers of the CYP2C9*3 allele, compared with 5% in noncarriers. A regression model showed a significant influence of CYP2C9*3 on the drug-drug interaction, predicting a warfarin dose reduction of 25% in CYP2C9*3 heterozygotes and 43% in CYP2C9*3 homozygotes. CONCLUSION: Our data indicate that the CYP2C9*3 polymorphism predisposes for a pharmacologic interaction between warfarin and simvastatin.
BACKGROUND:Simvastatin interacts with warfarin, but the strength of the interaction varies between individual patients, indicating a genetic predisposition. PATIENTS & METHODS: The influence of the CYP2C9*2 and CYP2C9*3 polymorphisms on the interaction between simvastatin and warfarin was analyzed in data from 1132 patients. RESULTS:Simvastatin use reduced warfarin dose requirements by 29% in carriers of the CYP2C9*3 allele, compared with 5% in noncarriers. A regression model showed a significant influence of CYP2C9*3 on the drug-drug interaction, predicting a warfarin dose reduction of 25% in CYP2C9*3 heterozygotes and 43% in CYP2C9*3 homozygotes. CONCLUSION: Our data indicate that the CYP2C9*3 polymorphism predisposes for a pharmacologic interaction between warfarin and simvastatin.
Authors: Sandhya Devarajan; Irene Moon; Ming-Fen Ho; Nicholas B Larson; Drew R Neavin; Ann M Moyer; John L Black; Suzette J Bielinski; Steven E Scherer; Liewei Wang; Richard M Weinshilboum; Joel M Reid Journal: Drug Metab Dispos Date: 2019-02-11 Impact factor: 3.922
Authors: Philip L Mar; Rakesh Gopinathannair; Brooke E Gengler; Mina K Chung; Arturo Perez; Jonathan Dukes; Michael D Ezekowitz; Dhanunjaya Lakkireddy; Gregory Y H Lip; Mike Miletello; Peter A Noseworthy; James Reiffel; James E Tisdale; Brian Olshansky Journal: Circ Arrhythm Electrophysiol Date: 2022-05-27