Comparative pharmacokinetics of voriconazole between elderly and young adult patients: a population pharmacokinetic study

Background: Voriconazole (VCZ) belongs to the class of broad-spectrum antifungal agents, and it is commonly used for the treatment of serious fungal infections. Safe and effective therapy with VCZ is a challenge due to the narrow therapeutic index and high variability in pharmacokinetics between patients. Age of the patients can be a significant factor for this variability. However, no prior study in Pakistan has compared the pharmacokinetics of VCZ among young and elderly patients. Methods: A population pharmacokinetic model was developed on NONMEM software by using therapeutic drug monitoring (TDM) data from 51 cancer patients. Patients were divided into two age groups, that is ≤ 65 years and > 65 years. The covariate influence on CL of VCZ was assessed by stepwise covariate modelling. The predictive performance and stability of the final model were evaluated by using goodness-of-fit plots and bootstrap analysis, respectively. Results: A one-compartment model with first-order elimination best described the data. The CL of VCZ in patients with age > 65 years was 3.11 L/h, which was significantly lower than the CL in patients with age ≤ 65 years, which was 6.46 L/h. No other covariate proved significant on CL and volume of distribution of VCZ. The final model demonstrated robust predictive performance and stability. Conclusions: The reduced CL of VCZ in elderly patients might be due to compromised hepatic enzymes in elderly patients. The dose of VCZ should be reduced in patients aged > 65 years.