biostudies-literatureUnknown24(1)Li X<h4>Background</h4>Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacokinetic equivalency of a test formulation and reference formulation (Vfend®) of Voriconazole.<h4>Materials and methods</h4>This was a randomized, open-label, single-dose, two-treatment, two-sequence, two-cycle, crossover phase I trial. The 48 subjects were equally divided into 4 mg/kg and 6 mg/kg groups. Within each group, the subjects were randomized 1:1 to the test or reference formulation.. After a 7-day washout period, crossover formulations were administered. The blood samples were collected at 0.5, 1.0, 1.33,1.42,1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 4 mg/kg group, while at 0.5, 1.0, 1.5, 1.75, 2.0, 2.08, 2.17, 2.33, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 6 mg/kg group. The plasma concentrations of Voriconazole were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The safety of the drug was evaluated.<h4>Results</h4>The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C_max, AUC_0-t, and AUC_0-∞ in both 4 mg/kg and 6 mg/kg groups were within the prespecified bioequivalence limits between 80 ~ 125%. In the 4 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C_max was (2.552 ± 0.448) μg/mL, AUC_0-t was (11.875 ± 7.157) h*μg/mL and AUC_0-∞ was (12.835 ± 9.813) h*μg/mL after a single dose of 4 mg/kg test formulation. The mean C_max was (2.615 ± 0.464) μg/mL, AUC_0-t was (12.500 ± 7.257) h*μg/mL and AUC_0-∞ was (13.416 ± 9.485) h*μg/mL after a single dose of 4 mg/kg reference formulation. In the 6 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C_max was (3.538 ± 0.691) μg/mL, AUC_0-t was (24.976 ± 12.364) h*μg/mL and AUC_0-∞ was (26.212 ± 14.057) h*μg/mL after a single dose of 6 mg/kg test formulation. The mean C_max was (3.504 ± 0.667) μg/mL AUC_0-t was (24.990 ± 12.455) h*μg/mL and AUC_0-∞ was (26.160 ± 13.996) h*μg/mL after a single dose of 6 mg/kg reference formulation. Serious adverse event (SAE) was not observed.<h4>Conclusion</h4>In both 4 mg/kg group and 6 mg/kg group, equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence for both test and reference formulations of Voriconazole.<h4>Trial registration</h4>NCT05330000 (15/04/2022).BMC pharmacology & toxicology14https://www.ebi.ac.uk/biostudies/studies/S-EPMC9985189biostudies-literaturePharmacokinetics and safety of two Voriconazole formulations after intravenous infusion in two doses in healthy Chinese subjects.PMC9985189Li XLiu YLin PLi TWang CShi PTao YHu HCao YFu YSun FLiu SfalsePharmacokinetics and safety of two Voriconazole formulations after intravenous infusion in two doses in healthy Chinese subjects.<h4>Background</h4>Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacokinetic equivalency of a test formulation and reference formulation (Vfend®) of Voriconazole.<h4>Materials and methods</h4>This was a randomized, open-label, single-dose, two-treatment, two-sequence, two-cycle, crossover phase I trial. The 48 subjects were equally divided into 4 mg/kg and 6 mg/kg groups. Within each group, the subjects were randomized 1:1 to the test or reference formulation.. After a 7-day washout period, crossover formulations were administered. The blood samples were collected at 0.5, 1.0, 1.33,1.42,1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 4 mg/kg group, while at 0.5, 1.0, 1.5, 1.75, 2.0, 2.08, 2.17, 2.33, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 6 mg/kg group. The plasma concentrations of Voriconazole were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The safety of the drug was evaluated.<h4>Results</h4>The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C_max, AUC_0-t, and AUC_0-∞ in both 4 mg/kg and 6 mg/kg groups were within the prespecified bioequivalence limits between 80 ~ 125%. In the 4 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C_max was (2.552 ± 0.448) μg/mL, AUC_0-t was (11.875 ± 7.157) h*μg/mL and AUC_0-∞ was (12.835 ± 9.813) h*μg/mL after a single dose of 4 mg/kg test formulation. The mean C_max was (2.615 ± 0.464) μg/mL, AUC_0-t was (12.500 ± 7.257) h*μg/mL and AUC_0-∞ was (13.416 ± 9.485) h*μg/mL after a single dose of 4 mg/kg reference formulation. In the 6 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C_max was (3.538 ± 0.691) μg/mL, AUC_0-t was (24.976 ± 12.364) h*μg/mL and AUC_0-∞ was (26.212 ± 14.057) h*μg/mL after a single dose of 6 mg/kg test formulation. The mean C_max was (3.504 ± 0.667) μg/mL AUC_0-t was (24.990 ± 12.455) h*μg/mL and AUC_0-∞ was (26.160 ± 13.996) h*μg/mL after a single dose of 6 mg/kg reference formulation. Serious adverse event (SAE) was not observed.<h4>Conclusion</h4>In both 4 mg/kg group and 6 mg/kg group, equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence for both test and reference formulations of Voriconazole.<h4>Trial registration</h4>NCT05330000 (15/04/2022).2023-01-01T00:00:00Z2023 Mar2026-05-29T01:16:48.155Z2025-02-18T23:35:24.594ZS-EPMC99851893686938710.1186/s40360-023-00652-3