p450 - publications

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1. Pharmacogenomics. 2012 May;13(7):757-62.

A clinically significant interaction between warfarin and simvastatin is unique
to carriers of the CYP2C9*3 allele.

Andersson ML, Eliasson E, Lindh JD.

Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical
Pharmacology, Karolinska University Hospital Huddinge, SE 141 86, Stockholm,

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. Original submitted 5 January 2012; Revision submitted
15 February 2012.

PMID: 22594507 [PubMed - in process]