Parametric population pharmacokinetics of linezolid: A systematic review.

Linezolid is often used for the infections caused by drug-resistant Gram-positive bacteria. Recent studies suggest that large between-subject variability (BSV) and within-subject variability could alter drug pharmacokinetics (PK) during linezolid therapy due to pathophysiological changes. This review synthesized information on linezolid population PK studies and summarized the significant covariates that influence linezolid PK. A literature search was performed using PubMed, Web of Science and Embase from their inception to 30 September 2021. Published studies were included if they contained data analysing linezolid PK parameters in humans using a population approach with a nonlinear mixed-effects model. Twenty-five studies conducted in adults and five in paediatrics were included. One- and two-compartment models were the commonly used structural models for linezolid. Body size (weight, lean body weight and body surface area), creatinine clearance (CLcr) and age significantly influenced linezolid PK. The median clearance (CL) values (ranges) in infants (0.128 L/h/kg [0.121-0.135]] and children (0.107 L/h/kg [0.088-0.151]] were higher than in adults (0.098 L/h/kg [0.044-0.237]]. For patients with severe renal impairment (CLcr ≤ 30 mL/min), the CL was 37.2% (15.2-55.3%) lower than in patients with normal renal function. The optimal linezolid dosage should be adjusted based on the patient's body size, renal function and age. More studies are needed to explore the exact mechanism of linezolid elimination and evaluate the PK characteristics in paediatric patients. © 2022 British Pharmacological Society.

Citation

Yan Qin, Li-Li Zhang, Yan-Rong Ye, Yue-Ting Chen, Zheng Jiao. Parametric population pharmacokinetics of linezolid: A systematic review. British journal of clinical pharmacology. 2022 Sep;88(9):4043-4066

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PMID: 35484096

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