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A Review of Population Pharmacokinetic Analyses of Linezolid
Clinical Pharmacokinetics ( IF 4.6 ) Pub Date : 2022-06-14 , DOI: 10.1007/s40262-022-01125-2
Enrique Bandín-Vilar 1, 2, 3 , Laura García-Quintanilla 1, 2, 3 , Ana Castro-Balado 1, 2, 3 , Irene Zarra-Ferro 1, 2 , Miguel González-Barcia 1, 2 , Manuel Campos-Toimil 4 , Víctor Mangas-Sanjuan 5, 6 , Cristina Mondelo-García 1, 2 , Anxo Fernández-Ferreiro 1, 2
Affiliation  

In recent years, many studies on population pharmacokinetics of linezolid have been conducted. This comprehensive review aimed to summarize population pharmacokinetic models of linezolid, by focusing on dosage optimization to maximize the probability of attaining a certain pharmacokinetic-pharmacodynamic parameter in special populations. We searched the PubMed and EMBASE databases for population pharmacokinetic analyses of linezolid using a parametric non-linear mixed-effect approach, including both observational and prospective trials. Of the 32 studies, 26 were performed in adults, four in children, and one in both adults and children. High between-subject variability was determined in the majority of the models, which was in line with the variability of linezolid concentrations previously detected in observational studies. Some studies found that patients with renal impairment, hepatic failure, advanced age, or low body weight had higher exposure and adverse reactions rates. In contrast, lower concentrations and therapeutic failure were associated with obese patients, young patients, and patients who had undergone renal replacement techniques. In critically ill patients, the inter-individual and intra-individual variability was even greater, suggesting that this population is at an even higher risk of underexposure and overexposure. Therapeutic drug monitoring may be warranted in a large proportion of patients given that the Monte Carlo simulations demonstrated that the one-size-fits-all labeled dosing of 600 mg every 12 h could lead to toxicity or therapeutic failure for high values of the minimum inhibitory concentration of the target pathogen. Further research on covariates, including renal function, hepatic function, and drug–drug interactions related to P-glycoprotein could help to explain variability and improve linezolid dosing regimens.



中文翻译:

利奈唑胺群体药代动力学分析综述

近年来,针对利奈唑胺的群体药代动力学进行了大量研究。本综合综述旨在总结利奈唑胺的群体药代动力学模型,重点关注剂量优化,以最大限度地提高在特殊人群中获得特定药代动力学-药效参数的可能性。我们使用参数非线性混合效应方法检索了 PubMed 和 EMBASE 数据库,以进行利奈唑胺的群体药代动力学分析,包括观察性试验和前瞻性试验。在 32 项研究中,26 项针对成人,4 项针对儿童,1 项针对成人和儿童。大多数模型都确定了受试者之间的高变异性,这与之前在观察性研究中检测到的利奈唑胺浓度的变异性一致。一些研究发现,肾功能不全、肝功能衰竭、高龄或体重过轻的患者的暴露率和不良反应率较高。相反,较低的浓度和治疗失败与肥胖患者、年轻患者和接受肾脏替代技术的患者相关。在危重患者中,个体间和个体内的变异性更大,表明该人群暴露不足和过度暴露的风险更高。鉴于蒙特卡洛模拟表明,每 12 小时 600 mg 的一刀切的标签剂量可能会导致毒性或治疗失败,因为最小抑制值较高目标病原体的浓度。对协变量(包括肾功能、肝功能以及与 P-糖蛋白相关的药物间相互作用)的进一步研究可能有助于解释变异性并改进利奈唑胺的给药方案。

更新日期:2022-06-14
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