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

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.

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.

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.

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.