Effects of liver and kidney function on occurrence of linezolid-induced thrombocytopenia and administration strategies based on population pharmacokinetics: a meta-analysis and systematic review
10.3760/cma.j.cn114015-20231220-00916
- VernacularTitle:肝肾功能对利奈唑胺致血小板减少症发生的影响及基于群体药物代谢动力学的给药策略：meta分析及系统评价
- Author:
Yating DENG
1
;
Liang DING
;
Kaixing WEI
;
Ziyun DUAN
;
Yaohui YUE
Author Information
1. 西安医学院基础医学部药理学与毒理学教研室，西安 710021
- Publication Type:Journal Article
- Keywords:
Renal insufficiency;
Hepatic insufficiency;
Linezolid;
Thrombocytopenia;
Meta-analysis;
System interview;
Population pharmacokinetics;
Dose optimization
- From:
Adverse Drug Reactions Journal
2024;26(6):337-346
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To systematically evaluate the effects of liver and kidney function on the occurrence of thrombocytopenia induced by linezolid and the population pharmacokinetic characteristics of linezolid, so as to provide guidance for the individualization of linezolid in patients with liver and renal insufficiency.Methods:Relevant databases at home and abroad have been searched up to November 2023. The literature about the influence of liver and kidney function on linezolid-induced thrombocytopenia were analyzed using the Rev Man 5.4 statistical software, and the effect sizes were odds ratio ( OR) and standardized mean difference ( SMD) with their 95% confidence interval ( CI) in the meta-analysis. The literature on population pharmacokinetic studies of linezolid were summarized and systematically reviewed. Results:A total of 32 literature were included in the meta-analysis, including 4 112 patients. Among them, 1 458 (35.5%) developed thrombocytopenia and 2 654 (64.5%) did not. The meta-analysis results showed that the risk of linezolid-induced thrombocytopenia in the renal insufficiency patients was higher than that in patients with normal renal function [47.9% (594/1 241) vs. 25.8% (493/1 912), OR=3.24, 95% CI: 2.31-4.53], and the lower baseline creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) were associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05); the risk of thrombocytopenia induced by linezolid in patients with liver dysfunction was higher than that in patients with normal liver function [47.6% (119/250) vs. 33.9% (360/1 061), OR=2.36, 95% CI: 1.73-3.22], and the higher baseline total bilirubin (TBil) was associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05). A total of 15 articles were included in the review of population pharmacokinetic study, 11 of which were based on self-built or publicly published population pharmacokinetic models and used Monte Carlo simulation to evaluate the efficacy and safety probabilities in different dosing regimens of linezolid. Among them, there were 5 and 2 articles optimized the dosing regimen of linezolid in patients with renal and liver insufficiency, respectively. Conclusions:Liver and renal insufficiency increases the risk of linezolid-induced thrombocytopenia, and baseline levels of Ccr, eGFR, and TBil can serve as sensitive indicators for predicting the risk. Patients with liver and renal insufficiency can use population pharmacokinetic models for an optimized linezolid regimen before treatment to reduce the risk of linezolid-induced thrombocytopenia.
