Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9506310.26442/2075-1753_2018.10.20-28ArticlesСтатьиResearch ArticleStatins pharmacogenetics: metabolizing enzymes and transporters polymorphisms roleФармакогенетика статинов: роль полиморфизмов метаболизирующих ферментов и транспортеровLeonovaM. VЛеоноваМарина Васильевна

чл.-кор. РАЕН, д-р мед. наук, проф., клинический фармаколог, член

anti23@mail.ruGaysenokO. VГайсенокОлег Владимирович

канд. мед. наук, зав. отд-нием общей кардиологии

ovgaisenok@fgu-obp.ruLeonovA. SЛеоновАнтон Сергеевич

врач-терапевт, клинический фармаколог

henry1214@mail.ruInterregional Public Organization «Russian Association of Clinical Pharmacologists»Межрегиональная общественная организация «Ассоциация клинических фармакологов России»Joint Hospital with Polyclinic of the Administrative Department of the President of the Russian FederationФГБУ ОТП151020182010VOL 20, NO10 (2018)ТОМ 20, №10 (2018)202828122021Copyright ©; 2018, Consilium MedicumCopyright ©; 2018, ООО "Консилиум Медикум"2018Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95063

The article presents a review of present data on pharmacogenetics role in statins pharmacokinetics and pharmacodynamics, their lipid-lowering activity and toxicity. The influence of genetic polymorphism of metabolizing ferments CYP3А4/5 and CYP2С9 on statins pharmacokinetics and effectiveness is shown. The influence of transporters (ОАТР and АВС families) on lipid-lowering activity and toxicity, particularly on confirmed association of SLCO1B1 polymorphism on statins pharmacokinetics as well as on risk of statin induced myopathy development after simvastatin or atorvastatin use that was reported in Food and Drug Administration guidelines is demonstrated. Р-glucoprotein and ABCG2 transporters also influence statins clinical effectiveness. The incidence of genetic polymorphism in Russian population is quite high, especially in OATP and ABC transporters, that can explain the use of medications in lower dosage than it is recommended for clinical practice. That is why the approaches for medication choices and dosage should be individualized for statin therapy optimization taking into account pharmacogenetic aspects.

Представлен научный обзор современных данных о роли фармакогенетики в фармакокинетике и фармакодинамике статинов, липидснижающей эффективности и токсичности. Показано влияние генетического полиморфизма метаболизирующих ферментов CYP3А4/5, CYP2С9 на фармакокинетику статинов и эффективность. Показано влияние транспортеров (семейства ОАТР и АВС) на липидснижающее действие и токсичность, в частности доказанную ассоциацию полиморфизма SLCO1B1 с фармакокинетикой статинов, а также риск развития статининдуцированной миопатии симвастатином, аторвастатином, что нашло отражение в рекомендациях Управления по контролю пищевых продуктов и лекарств в США. Транспортеры Р-гликопротеин и ABCG2 также влияют на клиническую эффективность статинов. Встречаемость генетического полиморфизма в российской популяции достаточно высока, особенно по транспортерам OATP и ABC (Р-гликопротеина), что может объяснять применение препаратов в меньших дозировках, чем рекомендовано для клинической практики. Поэтому для оптимизации фармакотерапии статинами следует индивидуализировать подходы выбора препаратов и доз с учетом фармакогенетических аспектов.

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