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EFFECT OF GENES SLCO1B1 AND MDR1 POLYMORPHISM ON ATORVASTATIN PHARMACOKINETICS AND PHARMACODYNAMICS IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA: RESULTS OF PILOT PHARMACOGENETICS STUDY

https://doi.org/10.20996/1819-6446-2008-4-2-47-50

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Abstract

Aim. To study effects of genes SLCO1B1 and MDR1 polymorphism on atorvastatin pharmacokinetics and pharmacodynamics in patients with primary hypercholesterolemia.

Material and methods. 21 patients (9 men and 14 women; 57 y.o. in average, all were Caucasians) with primary hypercholesterolemia (NCEP criteria) were involved in the study. All patients had total cholesterol plasma level >5.9 mmol/l after 4-week course of lipid-lowering diet. Atorvastatin (80 mg once daily in the first treatment day) was given to patients for pharmacokinetics estimation. Blood samples for analysis were taken before and after drug administration. Genes SLCO1B1 and MDR1 polymorphism screening was made by polymerase chain reaction.

Results. Treatment efficacy in patients with SLCO1B1.с521СС genotype was less than this in patients with other genotypes. Genes MDR1 polymorphism have no influence on treatment efficacy. There is no correlation between genotype and drug adverse effects rate.

Conclusion. Polymorphism of genes responsible for protein-transporters (first of all ОАТР-С) can significantly determine drug pharmacokinetic and individual response on atorvastatin therapy.

About the Authors

A. V. Semenov
Moscow Medical Academy named after I.M.Sechenov
Russian Federation
Department of clinical pharmacology and internal medicine propaedeutics


D. A. Sichev
Moscow Medical Academy named after I.M.Sechenov
Russian Federation
Department of clinical pharmacology and internal medicine propaedeutics


V. G. Kukes
Moscow Medical Academy named after I.M.Sechenov
Russian Federation
Department of clinical pharmacology and internal medicine propaedeutics


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For citation:


Semenov A.V., Sichev D.A., Kukes V.G. EFFECT OF GENES SLCO1B1 AND MDR1 POLYMORPHISM ON ATORVASTATIN PHARMACOKINETICS AND PHARMACODYNAMICS IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA: RESULTS OF PILOT PHARMACOGENETICS STUDY. Rational Pharmacotherapy in Cardiology. 2008;4(2):47-50. (In Russ.) https://doi.org/10.20996/1819-6446-2008-4-2-47-50

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)