Abstract

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.

Author Details

Authors

• Mustajab Ali Naseer¹
• Muhammad Aamir¹
• Hajira Bilal²
• Walaa F. Alsanie^{3, 4}
• Abdulhakeem S. Alamri^{3, 4}
• Muhammad Usman⁵

Departments

• ¹ Department of Pharmacy, The University of Lahore, Lahore, Pakistan,
• ² School of Health and Biomedical Sciences, STEM College, Bundoora West Campus, RMIT University, Australia,
• ³ Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences,
• ⁴ Research Center for Health Sciences, Taif University, Taif, Saudi Arabia, and
• ⁵ Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan

Address

Muhammad Usman, PhD
Institute of Pharmaceutical Sciences
University of Veterinary and Animal Sciences
Lahore, Pakistan
Email: [email protected]

Citation