Abstract
We evaluated effect of activity of cytochrome P450 CYP2C9 on maintenance doses of warfarin in 33 patients with implanted artificial heart valves. Losartan test was used for measurement of concentration of active metabolite E-3174 in urine. Concentration of E-3174 below 2500 ng/ml in patients with genotype CYP2C981/*1 with sensitivity 87% and specificity 66% predicted requirement of low doses (< 5 mg/day) of warfarin in the late postoperative period (odds ratio 14, 95% confidence interval 1.135 to 172.75).
MeSH terms
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Adult
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Anticoagulants / pharmacokinetics
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Aryl Hydrocarbon Hydroxylases* / genetics
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Aryl Hydrocarbon Hydroxylases* / metabolism
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Biotransformation / genetics
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Cardiovascular Agents / pharmacokinetics
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Cytochrome P-450 CYP2C9
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Dose-Response Relationship, Drug
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Drug Monitoring / methods
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Female
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Genotype
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Heart Valve Diseases* / drug therapy
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Heart Valve Diseases* / genetics
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Heart Valve Diseases* / surgery
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Heart Valve Prosthesis Implantation / methods*
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Humans
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Imidazoles / pharmacokinetics
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Imidazoles / urine
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Losartan / pharmacokinetics*
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Male
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Middle Aged
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Pharmacogenetics
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Polymorphism, Genetic
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Postoperative Period
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Tetrazoles / pharmacokinetics
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Tetrazoles / urine
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Warfarin / pharmacokinetics*
Substances
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Anticoagulants
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Cardiovascular Agents
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Imidazoles
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Tetrazoles
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Warfarin
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CYP2C9 protein, human
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Cytochrome P-450 CYP2C9
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Aryl Hydrocarbon Hydroxylases
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losartan carboxylic acid
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Losartan