Population pharmacokinetics of linezolid among post-operative patients: Implications for dosing strategies

Linezolid is a synthetic antibiotic and produces its antibacterial effect by inhibiting protein synthesis. It is used to treat life-threatening infections caused by MRSA and VRE. Linezolid clearance occurs through both the renal and hepatic routes. The identification of factors associated with linezolid clearance is required in Pakistani patients. A total of 215 samples from 59 post-operative patients were collected from a tertiary care hospital after a first dose of linezolid. The data was used to develop a population pharmacokinetic (popPK) model by using NONMEM® software. Analysis of the available covariates on pharmacokinetic parameters of linezolid was performed by using stepwise covariate modeling approach, A one-compartment model described the popPK and the value for linezolid clearance (CL) was 3.72 L/h while that of volume of distribution (Vd) was 36.9 L. The interindividual variability on linezolid CL was 36.5%. During stepwise covariate analysis, creatinine clearance (CRCL) was proved to be a significant covariate on CL. This is concluded that the clearance of linezolid is influenced by the renal status of patients and there is a dire need for dose optimization of linezolid in Pakistani patients based on renal status in order to avoid toxicity and adverse drug effects.