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Войти в исследования International journal of clinical pharmacology and therapeutics · 2026
Dose optimization of linezolid among surgical patients: A population pharmacokinetic study.
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Naseer Mustajab Ali, Aamir Muhammad, Bilal Hajira, Alsanie Walaa F, Alamri Abdulhakeem S, Usman Muhammad
Аннотация
BACKGROUND: Linezolid is classified under the reserve group of antibiotics, and it exerts its antibacterial activity by disrupting protein synthesis. Clinically, linezolid is used for treatment of severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). It is eliminated through both renal and hepatic routes. Being a narrow therapeutic index drug, linezolid needs special dosing considerations for safe and effective treatment.
MATERIALS AND METHODS: A plasma concentration dataset of 94 patients with 347 samples was used for development of a population pharmacokinetic model on NONMEM software. The influence of significant covariates on pharmacokinetic parameters was analyzed by stepwise covariate modeling, and dosing simulations were performed on the basis of significant covariates.
RESULTS: The data was best analyzed using a one-compartment model with first-order elimination. The clearance (CL) of linezolid was estimated as 3.38 L/h, while volume of distribution (Vd) was 36 L. The between-subject variability on linezolid CL was 29.8%, and that of Vd was 39.6%. Creatinine clearance (CrCl) and age of the patients were proven to be significant covariates on CL, while no significant covariate was observed for Vd during stepwise covariate modeling. The dosing simulations revealed that a different dose should be administered based on the CrCl of patients.
CONCLUSION: The renal status and age of the patients are significant covariates responsible for linezolid CL, and a dose of 200, 300, 400, and 600 mg is appropriate for patients with CrCl of 20, 40, 80, and 120 mL/min, respectively.
MATERIALS AND METHODS: A plasma concentration dataset of 94 patients with 347 samples was used for development of a population pharmacokinetic model on NONMEM software. The influence of significant covariates on pharmacokinetic parameters was analyzed by stepwise covariate modeling, and dosing simulations were performed on the basis of significant covariates.
RESULTS: The data was best analyzed using a one-compartment model with first-order elimination. The clearance (CL) of linezolid was estimated as 3.38 L/h, while volume of distribution (Vd) was 36 L. The between-subject variability on linezolid CL was 29.8%, and that of Vd was 39.6%. Creatinine clearance (CrCl) and age of the patients were proven to be significant covariates on CL, while no significant covariate was observed for Vd during stepwise covariate modeling. The dosing simulations revealed that a different dose should be administered based on the CrCl of patients.
CONCLUSION: The renal status and age of the patients are significant covariates responsible for linezolid CL, and a dose of 200, 300, 400, and 600 mg is appropriate for patients with CrCl of 20, 40, 80, and 120 mL/min, respectively.