Population Pharmacokinetics of Posaconazole Tablets and Monte Carlo Simulations To Determine whether All Patients Should Receive the Same Dose

• DOI: 10.1128/aac.01166-17
• Publication Date: 2017-08-29T00:30:26Z
• Authors: A. Petitcollin; C. Boglione-Kerrien; C. Tron; S. Nimubona; S. Lalanne; F. Lemaitre; E. Bellissant; M.-C. Verdier
• Keywords: Posaconazole

ABSTRACT Posaconazole is extensively used for prophylaxis invasive fungal infections. The gastro-resistant tablet formulation has allowed the bioavailability issues encountered with oral suspension to be overcome. However, overexposure now frequent. This study aimed (i) describe pharmacokinetics of posaconazole tablets in a real-life cohort patients hematological malignancies and (ii) perform Monte Carlo simulations assess possibility that daily dose can reduced while keeping sufficient exposure. Forty-nine consecutive inpatients were prospectively included study. trough concentrations (TC) measured once week, biological demographic data collected. analyzed by compartmental modeling, performed using estimated parameters rate attainment target TC after reduction. well described one-compartment model first-order absorption elimination. values (interindividual variabilities) as follows: constant ( k ) was 0.588 h −1 (fixed), volume distribution V / F 420 liters (28.2%), clearance (CL/ 7.3 liters/h (24.2%) 31.9% interoccasion variability. percent simulated had at steady state ≥1.5 μg/ml maintained above 1 reduction 200 mg daily. A third these eligible soon 48 treatment. Though less impacted than suspension, remain highly variable. Simulations showed approximately half would benefit from 300 minimal recommended 0.7 μg/ml, resulting 33% savings cost this very expensive drug.