Population Pharmacokinetics of Voriconazole and Dose Optimization in Elderly Chinese Patients

Abstract

Voriconazole is commonly recommended as a first-line therapy for invasive aspergillosis infections. Elderly patients are susceptible to infectious diseases owing to their decreased physical function and immune system. Our study aims to establish a population pharmacokinetics model for elderly patients receiving intravenous voriconazole, and to optimize dosing protocols through a simulated approach. An accurate fit to the concentration-time profile of voriconazole was achieved by employing a 1-compartment model featuring first-order elimination. The typical clearance rate of voriconazole was found to be 3.22 L/h, with a typical volume of distribution of 194 L. The covariate analysis revealed that albumin (ALB), gamma-glutamyl transpeptidase, and direct bilirubin had significant impacts on voriconazole clearance. Additionally, body weight was found to be associated with the volume of distribution. Individualized dosing regimens were recommended for different ALB levels based on population pharmacokinetics model prediction. The proposed dosing regimens could provide a rationale for dosage individualization, improve the clinical outcomes, and minimize drug-related toxicities.

Keywords: Monte Carlo simulation; dosage optimization; elderly patients; population pharmacokinetics; voriconazole.