Безопасность антибактериальных препаратов при трансплантации печени: обзор фармакокинетических фармакодинамических аспектов

ВВЕДЕНИЕ. Изменения функции печени и почек, системное воспаление и иммуносупрессивная терапия у реципиентов печени существенно модифицируют фармакокинетический и фармакодинамический профиль антибактериальных препаратов, что требует оптимизации подходов к их применению.

ЦЕЛЬ. Систематизировать данные о фармакокинетических и фармакодинамических особенностях и потенциале межлекарственных взаимодействий антибактериальных препаратов у пациентов после трансплантации печени для уточнения профиля безопасности антибактериальной терапии.

ОБСУЖДЕНИЕ. Анализ данных литературы показал, что частота инфекционных осложнений после трансплантации печени достигает 41,3%, при этом до 21,7% случаев обусловлены полирезистентными штаммами. В раннем посттрансплантационном периоде изменения объема распределения, связывания с белками плазмы крови и клиренса антибактериальных препаратов обусловливают вариабельность системной экспозиции и затрудняют достижение целевых фармакокинетических/фармакодинамических показателей, повышая риск неэффективности и токсичности терапии. Клинически значимые межлекарственные взаимодействия между макролидами (кларитромицин, эритромицин) и ингибиторами кальциневрина (такролимус, циклоспорин), а также ингибиторами мишени рапамицина млекопитающих (сиролимус, эверолимус) сопровождаются повышением концентраций иммунодепрессантов и увеличением риска токсических реакций. Основными нежелательными реакциями являются гепатотоксичность, нефротоксичность, гематологические и неврологические осложнения, риск которых возрастает при полипрагмазии и нарушении функции почек.

ВЫВОДЫ. Фармакокинетическая и фармакодинамическая вариабельность антибактериальных препаратов у реципиентов трансплантата печени определяют необходимость персонализированного подхода. Использование терапевтического лекарственного мониторинга β-лактамных антибиотиков, ванкомицина, аминогликозидов, линезолида и учет межлекарственных взаимодействий может повысить эффективность и безопасность антибактериальной терапии у пациентов после трансплантации печени.

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