safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2026-586safetyrisk-586Research ArticleСтатьиБезопасность антибактериальных препаратов при трансплантации печени: обзор фармакокинетических фармакодинамических аспектовSafety of Antibacterial Agents in Liver Transplantation: A Review of Pharmacokinetic and Pharmacodynamic Aspectshttps://orcid.org/0009-0007-3617-5688ИсаковаА. А.IsakovaA. A.

Исакова Анастасия Александровна

ул. Трубецкая, д. 8, стр. 2, Москва, 119991; шоссе Энтузиастов, д. 86, стр. 6, Москва, 111123

Anastasia A. Isakova

8/2 Trubetskaya St., Moscow 119991; 86/6 Entuziastov Hwy., Moscow 111123

isakova_a_a@student.sechenov.ruhttps://orcid.org/0000-0002-8602-514XАлихановР. Б.AlikhanovR. B.

Алиханов Руслан Богданович, д-р мед. наук

шоссе Энтузиастов, д. 86, стр. 6, Москва, 111123

Ruslan B. Alikhanov, Dr. Sci. (Med.)

86/6 Entuziastov Hwy., Moscow 111123

r.alikhanov@mknc.ruhttps://orcid.org/0009-0002-8881-0499ГасиеваО. Ю.GasievaO. Yu.

Гасиева Ольга Юрьевна

шоссе Энтузиастов, д. 86, стр. 6, Москва, 111123

Olga Yu. Gasieva

86/6 Entuziastov Hwy., Moscow 111123

olga.gasieva89@gmail.comhttps://orcid.org/0009-0001-0484-189XМатвееваЮ. А.MatveevaJ. A.

Матвеева Юлия Александровна

шоссе Энтузиастов, д. 86, стр. 6, Москва, 111123

Julia A. Matveeva

86/6 Entuziastov Hwy., Moscow 111123

Juli1424@yandex.ruhttps://orcid.org/0000-0001-6528-1585ЛазареваН. Б.LazarevaN. B.

Лазарева Наталья Борисовна, д-р мед. наук, доцент

ул. Трубецкая, д. 8, стр. 2, Москва, 119991

Natalia B. Lazareva, Dr. Sci. (Med.), Associate Professor

8/2 Trubetskaya St., Moscow 119991

lazareva_n_b@staff.sechenov.ruФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет); Государственное бюджетное учреждение здравоохранения города Москвы «Московский клинический научно-практический центр имени А.С. Логинова Департамента здравоохранения города Москвы»РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University); Moscow Clinical Scientific and Practical Center named after A. S. Loginov of the Department of Healthcare of the City of MoscowRussian FederationГосударственное бюджетное учреждение здравоохранения города Москвы «Московский клинический научно-практический центр имени А.С. Логинова Департамента здравоохранения города Москвы»РоссияMoscow Clinical Scientific and Practical Center named after A. S. Loginov of the Department of Healthcare of the City of MoscowRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation20260710202600Online First586Copyright © Исакова А.А., Алиханов Р.Б., Гасиева О.Ю., Матвеева Ю.А., Лазарева Н.Б., 20222022Исакова А.А., Алиханов Р.Б., Гасиева О.Ю., Матвеева Ю.А., Лазарева Н.Б.Isakova A.A., Alikhanov R.B., Gasieva O.Y., Matveeva J.A., Lazareva N.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/586ВВЕДЕНИЕ

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

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

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

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.

INTRODUCTION

INTRODUCTION. Alterations in hepatic and renal function, systemic inflammation, and immunosuppressive therapy in liver transplant recipients significantly modify the pharmacokinetic and pharmacodynamic profiles of antibacterial agents, necessitating optimization of their dosing strategies.

AIM

AIM. To systematize the available evidence on the pharmacokinetic and pharmacodynamic characteristics and drug–drug interaction potential of antibacterial agents in patients after liver transplantation in order to clarify the safety profile of antibacterial therapy.

DISCUSSION

DISCUSSION. The literature analysis demonstrated that the incidence of infectious complications after liver transplantation reaches 41.3%, with up to 21.7% of cases being caused by multidrug-resistant strains. In the early posttransplant period, changes in the volume of distribution, plasma protein binding, and clearance of antibacterial agents determine the variability of systemic exposure and hinder the attainment of pharmacokinetic and pharmacodynamic targets, increasing the risk of treatment failure and drug toxicity. Clinically significant drug–drug interactions between macrolides (clarithromycin, erythromycin) and calcineurin inhibitors (tacrolimus, cyclosporine) as well as inhibitors of the mechanistic target of rapamycin (mTOR) (sirolimus, everolimus) are associated with increased concentrations of immunosuppressants and an increased risk of toxic reactions. The principal adverse reactions are hepatotoxicity, nephrotoxicity, and hematologic and neurologic complications, the risk of which increases with polypharmacy and impaired renal function.

CONCLUSIONS

CONCLUSIONS. The pharmacokinetic and pharmacodynamic variability of antibacterial agents in liver transplant recipients necessitates a personalized approach. The use of therapeutic drug monitoring of β-lactam antibiotics, vancomycin, aminoglycosides, and linezolid, along with the consideration of drug–drug interactions, can improve the efficacy and safety of antibacterial therapy in patients after liver transplantation.

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