Pharmacokinetics and Bioequivalence Evaluation of Two Voriconazoletablets: an Open-Label, Single-Dose, Randomized, Two-Way CrossoverStudy in Healthy Chinese Male Volunteers

The aim of this study was to assess and compare the pharmacokinetic properties, bioavailability, and bioequivalence of a newly developed tablet of voriconazole with those of an established branded formulation in healthy Chinese adult male volunteers. An open-label, single-dose, randomized, 2-way crossover study was conducted in fasted healthy Chinese male volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive one tablet (200 mg) of the test or reference formulations, followed by a 1-week washout period and administration of the alternate formulations. Plasma samples were collected over 36 hours and analyzed by HPLC. The Voriconazole plasma concentrationi?½time curves were used to obtain pharmacokinetic parameters including AUC0i?½t, AUC0i?½∞, Cmax and Tmax. The criteria for bioequivalence were 90% CIs of 80% to 125% for AUC and 70% to 143% for Cmax, and no significant differences for Tmax with a non-parameter test, according to guidelines of the SFDA of China. Tolerability was based on the recording of adverse events (AEs). A total of 19 volunteers were included in the study. The mean (SD) Cmax, Tmax, AUC0i?½t, and AUC0i?½∞ values after administration of the test and reference formulation, respectively, were as follows: 925.73(356.11) versus 1040.25(448.93) ng/mL, 1.57(0.98) versus 1.38(0.96) hours, 5304.97(3072.25) versus 5141.63(2976.92) ng/mL/h, and 5783.21(3266.86) versus 5520.69(3148.42) ng/mL/h. The relative bioavailability of the test formulation was 103.2% by mean AUC0i?½t and 104.8% by mean AUC0−∞. The 90% CIs for the ratios of Cmax, AUC0i?½t, and AUC0−∞ were 77.3% to 122.7%, 85.7% to 114.3%, and 83.6% to 116.4%, respectively, meeting the predetermined criteria for bioequivalence. No drug-related AEs were observed. In this study the test and reference formulations had similar PK parameters and similar plasma concentration-time profiles and the test formulations met the regulatory criteria for bioequivalence to the established reference formulations based on the rate and extent of absorption. Both formulations were well tolerated.