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Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9) polymorphism with bleeding complication

¹ Marion Bessin Liver Research Center and Department of Medicine, Albert Einstein College of Medicine, New York, USA
² Department of Medicine, Albert Einstein College of Medicine, New York, USA
³ Department of Pharmacological Sciences, University of Newcastle Medical School, Newcastle upon Tyne, UK
⁴ Marion Bessin Liver Research Center and Departments of Medicine and Pathology, Albert Einstein College of Medicine, New York, USA

Correspondence to:
Correspondence to:
Dr Sanjeev Gupta
Albert Einstein College of Medicine, Ullmann Building, Room 625, 1300 Morris Park Avenue, Bronx, New York 10461, USA; sanjvgupta{at}pol.net

ABSTRACT
Drug metabolism may be perturbed by genetically determined differences in the metabolic activity of cytochrome P450 enzymes. The authors encountered extensive bleeding in a patient receiving warfarin for anticoagulation after the introduction of celecoxib, an anti-inflammatory drug. As the CYP2C9 enzyme metabolises these drugs, it was determined whether variant alleles were responsible for altering warfarin handling. Genetic analysis established that the patient was a compound heterozygote with CYP2C9*2 and *3 variant alleles, which exhibit lower drug metabolising capacity and enhance susceptibility to drug toxicity.

Keywords: warfarin; celecoxib; interaction; bleeding; CYP2C9; polymorphism; allele

Abbreviations: bp, base pair; COX, cyclo-oxygenase; INR, international normalised ratio; PCR, polymerase chain reaction

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