Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis
Wael A. Alghamdi, Mohammad H. Al‐Shaer, Guohua An, Abdullah Alsultan, Maia Kipiani, Ketevan Barbakadze, Lali Mikiashvili, David Ashkin, David E. Griffith, J. Peter Cegielski, Russell R. Kempker, Charles A. Peloquin
Abstract
The prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an f AUC (area under the unbound drug concentration-time curve)/MIC ratio of >119 as the PK/pharmacodynamic (PD) target and minimum (trough) concentrations of drug ( C min s) of 2 and 7 mg/liter as thresholds for toxicity.