CYP2C9 genetic variants and losartan oxidation in a Turkish population

Cytochrome P(450) 2C9 (CYP2C9) is a polymorphic enzyme catalysing the metabolism of several important drugs. Losartan has recently been suggested as a selective probe for CYP2C9 metabolic activity. The aim of the study was to determine the activity of CYP2C9, using losartan as a probe drug, in relat...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2004-07, Vol.60 (5), p.337-342
Main Authors: BABAOGLU, Melih O, YASAR, Umit, SANDBERG, Mia, ELIASSON, Erik, DAHL, Marja-Liisa, KAYAALP, S. Oguz, BOZKURT, Atila
Format: Article
Language:English
Subjects:
Adult
Antihypertensive agents
Antihypertensive Agents - adverse effects
Antihypertensive Agents - metabolism
Antihypertensive Agents - urine
Antihypertensive Agents/adverse effects/metabolism/urine
Aryl Hydrocarbon Hydroxylases - genetics
Aryl Hydrocarbon Hydroxylases - metabolism
Aryl Hydrocarbon Hydroxylases/genetics/metabolism
Biological and medical sciences
Cardiovascular system
Chromatography, High Pressure Liquid
Cytochrome P-450 CYP2C9
Female
Genetics, Population
Genotype
Humans
Losartan - adverse effects
Losartan - metabolism
Losartan - urine
Losartan/adverse effects/metabolism/urine
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Phenotype
Polymorphism, Genetic
Turkey
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Summary:Cytochrome P(450) 2C9 (CYP2C9) is a polymorphic enzyme catalysing the metabolism of several important drugs. Losartan has recently been suggested as a selective probe for CYP2C9 metabolic activity. The aim of the study was to determine the activity of CYP2C9, using losartan as a probe drug, in relation to CYP2C9 genotype in healthy Turkish subjects. A single oral dose of 25 mg losartan was given to 85 Turkish unrelated subjects. Concentrations of losartan and its carboxylic acid metabolite, E3174, were analysed by means of high-performance liquid chromatography in urine collected for 8 h. The CYP2C9 genotypes were determined in 85 subjects using polymerase chain reaction-based endonuclease digestion methods specific for CYP2C9*2 and *3. Losartan oxidation was also studied in vitro, using human CYP2C8 and CYP2C9 enzymes expressed in yeast. The frequencies of the allelic variants CYP2C9*2 and CYP2C9*3 were 0.100 and 0.088, respectively. The urinary losartan/E3174 ratio was significantly higher in subjects with CYP2C9*1/*3 genotype (median 2.35, n=12) than in subjects with CYP2C9*1/*1 (0.71, n=58) and *1/*2 (0.85, n=10) genotypes ( P
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-004-0785-5