title: Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis.
abstract: 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). 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 of >0.7 μg/ml. Average steady-state plasma concentrations were 61% lower in CF patients (0.233 μg/ml) than in non-CF LTRs (0.594 μg/ml; P = 0.03). The average dose-normalized plasma area-under-the-curve (AUC) values were also lower in CF (0.007 h·μg/ml) than in non-CF LTRs (0.02 h·μg/ml; P = 0.02). The weight-normalized apparent oral clearance values were 2.51 and 0.74 liters/h/kg among CF and non-CF LTRs, respectively (P = 0.005). Despite significant interpatient variability, plasma trough concentrations were strongly correlated with posaconazole AUC across all LTRs (r(2) = 0.95, P < 0.0001). Taken together, our study highlights a critical need to incorporate new formulations of posaconazole into prophylaxis and treatment strategies for LTRs, particularly those with CF. Future pharmacokinetic studies of both tablet and intravenous formulations must consider LTR-specific factors and incorporate a therapeutic drug monitoring plan in this patient population.
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Rujuta
authors.initials: R
authors.lastname: Joshi
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Wenchen
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Ensor
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA rv@pitt.edu.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000601:surgery; D005260:Female; D006801:Humans; D000072742:Invasive Fungal Infections / Q000517:prevention & control*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole