Pharmacokinetics and Safety of Two Voriconazole Formulations after Intravenous Infusion in Healthy Korean Volunteers

초록

Background: Voriconazole, a triazole antifungal agent exhibits broad-spectrum antifungal activity. It is used to treat severe, invasive fungal infections, including invasive aspergillosis and candidemia. The aim of this study was to assess the pharmacokinetic equivalence of a test formulation (Vorico (R) Injection) and reference formulation (Vfend (R) IV) of voriconazole. Materials and Methods: This was a randomized, open-label, single-dose, three-group, two-treatment, two-sequence, two-period, crossover phase I trial with 7-day washout periods (ClinicalTrials.gov identifier NCT02631954). Twenty-four healthy Korean male subjects were recruited. In each group, eight subjects were randomized in a 1:1 manner to receive a single dose of 200 mg test or reference formulation intravenously over 1.5 h. Blood samples were collected over 24 h post-dose, and plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a non-compartmental analysis, and safety was evaluated. Results: Twenty-three subjects completed the study. The geometric mean ratio (90% confidence interval) of the test formulation to reference formulation was 0.9570 (0.8178 - 1.1199) for the maximum plasma concentration (C-max) and 1.0720 (1.0262 - 1.1198) for the area under the concentration-time curve from dosing to the last quantifiable concentration (AUC(last)). The mean plasma concentration-time profiles, pharmacokinetic parameters, and safety were comparable between the two formulations. Conclusion: Equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence and similar safety profiles were observed for both test and reference formulations of voriconazole.

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