Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis

Invasive fungal infections (IFIs) are common among lung transplant recipients (LTRs). Posaconazole is an important antifungal agent for both prophylaxis and treatment of IFIs; however, detailed pharmacokinetic data are limited among LTRs, particularly those with cystic fibrosis (CF), are limited. Our objective was to conduct a pharmacokinetic study of posaconazole oral suspension among LTRs, with particular attention to patients with CF. We enrolled 20 LTRs, 7 with CF and 13 with other underlying lung diseases. Average daily doses in CF and non-CF patients were 829 and 862 mg, respectively. After ≥ 5 days of treatment, only 4 patients had average plasma concentrations >0.7 μg/mL. Average steady-state plasma concentrations were 61% lower in CF patients (0.233 μg/mL) compared to non-CF LTRs (0.594 μg/mL; P =0.03). Average dose normalized plasma area under curve were also lower in CF (0.007 h*μg/mL) compared to non-CF LTRs (0.02 h*μg/mL; P =0.02). Weight normalized apparent oral clearance was 2.51 and 0.74 L/h/kg among CF and non-CF LTRs, respectively ( P =0.005). Despite significant inter-patient variability, plasma trough concentrations were strongly correlated with posaconazole AUC across all LTRs (r 2 = 0.95, P