Evaluation of Posaconazole Pharmacokinetics in Adult Patients with Invasive Fungal Infection

Abstract

Mortality and morbidity due to invasive fungal infections have increased over the years. Posaconazole is a second-generation triazole agent with an extended spectrum of activity, which shows a high interindividual variability in its plasma levels, rendering dosing in many patients inconsistent or inadequate. Hence, posaconazole therapeutic drug monitoring, which is easily available in clinical practice, may improve treatment success and safety. The aim of the study was to describe posaconazole pharmacokinetics, and to evaluate the utility of therapeutic drug monitoring for therapy and prophylaxis in a cohort of adult patients. A fully validated chromatographic method was used to quantify posaconazole concentration in plasma collected from adult patients at the end of the dosing interval. Associations between variables were tested using the Pearson test. The Mann-Whitney test was used to probe the influence of categorical variables on continuous ones. A high inter-individual variability was shown. Of the 172 enrolled patients, among those receiving the drug by the oral route (N = 170), gender significantly influenced drug exposure: males showed greater posaconazole concentration than females (p = 0.028). This study highlights the importance of therapeutic drug monitoring in those with invasive fungal infections and its significant clinical implications; moreover we propose, for the first time, the possible influence of gender on posaconazole exposure.

Keywords: HPLC; antifungal; invasive fungal infections (IFIs); therapeutic drug monitoring (TDM); triazoles.

Figure 1

Plots of gender influence on posaconazole trough concentration, considering all the 172 enrolled patients (p = 0.028). Boxes and black lines in boxes represent respectively interquartile ranges (IQR) and median values; open dots and stars represent outlier values. Median values (horizontal line), interquartile range (IQR, bars), patient values (black square), highest and lowest value (whiskers) are shown. Males (N = 96) had 521.50 ng/mL (IQR: 256.00–240.25 ng/mL) median concentrations; Females (N = 76) had 376.50 ng/mL (IQR: 240.25–376.50 ng/mL) median concentrations.