ВПЛИВ SARS-CoV-2 НА ЦИТОХРОМ P450-ЗАЛЕЖНИЙ МЕТАБОЛІЗМ ЛІКАРСЬКИХ ПРЕПАРАТІВ: ОГЛЯД
DOI:
https://doi.org/10.31861/biosystems2025.02.238Ключові слова:
вірус, печінка, COVID-19, цитохром Р450, інфекція SARS-CoV-2, ксенобіотикиАнотація
Коронавірусна хвороба 2019 року (COVID-19) спричинена важким гострим респіраторним синдромом коронавірусу 2 (SARS-CoV-2) – вірусом, поширеним у всьому світу. Окрім ураження клітин дихальної системи, SARS-CoV-2 уражає органи травної системи, зокрема печінку. Встановлено, що COVID-19, спричинений SARS-CoV-2, суттєво впливає на функцію печінки у інфікованих пацієнтів, що є критично важливим для фармакокінетики та безпеки ліків. На клітини печінки SARS-CoV-2 може впливати як безпосередньо (через вірусний рецептор ангіотензинперетворюючого ферменту 2 (АПФ2)), так і опосередковано, включаючи вивільнення цитокінів та «цитокіновий шторм». Дія вірусу призводить до підвищення рівня печінкових ферментів (АЛТ, АСТ, ГГТ, ЛФ), зниження рівня альбуміну та порушення метаболізму ендогенних речовин та ксенобіотиків. Показано, що внаслідок пошкодження печінки порушується функціонування системи, яка метаболізує ксенобіотики (монооксигеназної системи або системи цитохрому P450 (CYP)). Дисфункціонування монооксигеназної системи, у свою чергу, призведе до зміни метаболізму ліків та додаткової інтоксикації організму, особливо у разі лікарської взаємодії. В огляді висвітлено основні потенційні механізми пошкодження печінки при COVID-19, що підвищить усвідомлення напрямку метаболізму ліків. Проаналізовані шляхи метаболізму протикоронавірусних препаратів різними ізоформами цитохрому P450 допоможуть запобігти взаємодії ліків у пацієнтів із супутніми захворюваннями.
Показано, що інфекція SARS-CoV-2 також змінює експресію CYP, зокрема CYP3A4, CYP2B6 та CYP2C9, через цитокін-опосередковану регуляцію, що призводить до зниження метаболізму ліків, підвищення їх концентрації у плазмі та вищого ризику токсичності. Поліпрагмазія при COVID-19, включаючи противірусні препарати, гідроксихлорохін, протизапальні засоби та препарати від супутніх захворювань, ще більше підвищує ризик взаємодії ліків та ураження печінки. Антицитокінова терапія (наприклад, тоцилізумаб) та допоміжні засоби, такі як мелатонін та вітамін D, можуть допомогти відновити активність CYP, зменшити запалення та покращити кліренс ліків. Розуміння механізмів дисфункції печінки, спричиненої вірусом SARS-CoV-2, та модуляції CYP є важливим для оптимізації фармакотерапії, мінімізації токсичності, пов'язаної з ліками, та покращення клінічних результатів у пацієнтів з COVID-19.
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