phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»phkinetica-206Research ArticleТЕОРЕТИЧЕСКИЕ ОСНОВЫTHEORETICAL BASISПоловые различия в биотрансформации лекарственных средств: значение для проведения клинических исследований лекарственных средствСычёвД. А.clinvest@mail.ruРаменскаяГ. В.clinvest@mail.ruКукесВ. Г.clinvest@mail.ruМосковская медицинская академия имени И.М.Сеченова, Институт клинической фармакологии НЦ «ЭСМП» МЗ РФRussian Federation20051104202001Клиническая фармакокинетика1517Copyright © Сычёв Д.А., Раменская Г.В., Кукес В.Г., 20202020Сычёв Д.А., Раменская Г.В., Кукес В.Г.Сычёв Д.А., Раменская Г.В., Кукес В.Г.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/206

Долгое время клинические исследования лекарственных средств I и II фазы у женщин не проводились, что было связано с опасениями негативного воздействия на возможную беременность и плод. Это привело к тому, что половые различия в фармакокинетике многих лекарственных средств (ЛС) стали изучаться только в последние 10 лет. Выяснилось, что особенно выражены половые различия в процессе биотрансформации ЛС. Результаты множества исследований говорят о том, что интенсивность метаболизма ЛС-субстратов изофермента цитохрома Р-450 3А4 (CYP3A4) выше у женщин, чем у мужчин. Следствием этого является более высокий метаболический клиренс данных ЛС у женщин по сравнению с мужчинами. Долгое время считалось, что эти различия обусловлены различной активностью CYP3A4 у женщин и мужчин. Так активность CYP3A4 у женщин, в среднем, на 40% выше, чем у мужчин. Повышенную активность CYP3A4 у женщин объясняли индуцирующей способностью эстрогенов и прогестерона, которые, как полагают, стимулируют экспрессию гена этого изофермента. Однако экспериментальных работ, подтверждающих это предположение, недостаточно.

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