rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2008-4-2-47-50rpcardio-1092Research ArticleORIGINAL STUDIESОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯEFFECT OF GENES SLCO1B1 AND MDR1 POLYMORPHISM ON ATORVASTATIN PHARMACOKINETICS AND PHARMACODYNAMICS IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA: RESULTS OF PILOT PHARMACOGENETICS STUDYВЛИЯНИЕ ПОЛИМОРФИЗМА ГЕНОВ SLCO1B1 И MDR1 НА ФАРМАКОКИНЕТИКУ И ФАРМАКОДИНАМИКУ АТОРВАСТАТИНА У ПАЦИЕНТОВ С ПЕРВИЧНОЙ ГИПЕРХОЛЕСТЕРИНЕМИЕЙ. РЕЗУЛЬТАТЫ ПИЛОТНОГО ФАРМАКОГЕНЕТИЧЕСКОГО ИССЛЕДОВАНИЯСеменовА. В.SemenovA. V.

Кафедра клинической фармакологии и пропедевтики внутренних болезней

Department of clinical pharmacology and internal medicine propaedeutics

СычевД. А.SichevD. A.

Кафедра клинической фармакологии и пропедевтики внутренних болезней

Department of clinical pharmacology and internal medicine propaedeutics

КукесВ. Г.KukesV. G.

Кафедра клинической фармакологии и пропедевтики внутренних болезней

Department of clinical pharmacology and internal medicine propaedeutics

Московская медицинская академия им. И.М. СеченоваРоссияMoscow Medical Academy named after I.M.SechenovRussian Federation200829012016424750Copyright © Semenov A.V., Sichev D.A., Kukes V.G., 20162016Семенов А.В., Сычев Д.А., Кукес В.Г.Semenov A.V., Sichev D.A., Kukes V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/1092Aim

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

Material and methods

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

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

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

Цель

Цель. Оценить влияние полиморфизма генов SLCO1B1 и MDR1 на фармакокинетику и фармакодинамику аторвастатина у пациентов с первичной гиперхолестеринемией. Материал и методы. В исследовании принял участие 21 пациент (9 мужчин и 14 женщин; средний возраст 57 лет; все – европеоидной расы) с первичной гиперхолестеринемией (по критериям NCEP) с концентрацией общего холестерина крови более 5,9 ммоль/л после 4-недельной гиполипидемической диеты. Для оценки фармакокинетики в первый день лечения пациентам назначался аторвастатин в дозе 80 мг с забором проб крови до (0) и после приема препарата. Проведен скрининг на наличие полиморфизма генов MDR1 и SLCO1B1 с помощью полимеразной цепной реакции.

Результаты

Результаты. Выявлена меньшая эффективность лечения у носителей генотипа SLCO1B1 .с521СС по сравнению с другими генотипами, тогда как полиморфизм гена MDR1 существенно не влиял на эффективность лечения. Не было выявлено связи между генотипом и частотой развития нежелательных лекарственных реакций.

Заключение

Заключение. Носительство полиморфных аллелей генов, кодирующих белки-транспортеры лекарственных средств (в первую очередь ОАТР-С) может существенно изменять фармакокинетические параметры (AUC) аторвастатина и индивидуальный ответ на лечение.

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The authors declare that there are no conflicts of interest present.