The Safety, Toleration, and Pharmacokinetics of Two Intravenous Voriconazole Formulations in Healthy Chinese Volunteers After Increasing Dose Administrations.

Sulfobutyl ether-beta-cyclodextrin sodium salt contained in the marketed intravenous voriconazole injection as a solubilizer may cause harmful accumulations. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of two intravenous voriconazole formulations containing excipients from different manufacturers using increasing dose administrations in healthy Chinese volunteers. A randomized, double-blind, placebo-controlled trial was conducted in three cohorts with 42 healthy Chinese volunteers. Each cohort of 14 volunteers was allocated in proportion (8:4:2) to test the formulation, reference voriconazole, or placebo successively by single-dose then multiple-dose administrations of 3, 4, and 6 mg/kg. Forty-one volunteers completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability (coefficient of variance of Cmax up to 68.0%, AUC0-τ up to 70.2%, and nonlinear PKs with a regression coefficient of Cmax  = 1.31 and AUC0-τ  = 1.75 in a single dose). In the steady state, RAuc of the test drug versus reference drug of the 3, 4, and 6 mg/kg dose group were 5.2 and 5.3, 5.6 and 6.3, and 5.8 and 5.5, respectively, and Rcmax were 2.5 and 2.7, 2.6 and 3.1, and 2.8 and 2.6, respectively. Eighty-three adverse events with 37 transient visual disturbances were mild. PKs with high interindividual variability, nonlinear characteristics, and significant dose-dependent accumulation were comparable between the two formulations. Overall, the safety of the test formulation was acceptable.

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study.

OBJECTIVES: To evaluate the pharmacokinetic properties and safety of empagliflozin, and the bioequivalence of test formulation empagliflozin tablet compared with the brand-name drug Jardiance (reference formulation) after single oral administration under fasting and fed conditions in healthy Chinese subjects. METHODS: An open-label randomized single-dose two-sequence, two-treatment, two-period crossover study was conducted in healthy Chinese subjects, with 30 subjects under fasting condition and another 30 subjects under fed condition. Under each condition, subjects received a single oral administration of either the test or reference empagliflozin formulation, and then they received a single oral dose of the other formulation after a 7-day washout period. RESULTS: A total of 29 subjects under each condition completed the study. The maximum plasma drug concentration, the area under the plasma concentration-time curve (AUC) from 0 to t (AUC0-t ), and the AUC from 0 to infinity (AUC0-∞ ) of test formulation and reference formulation was 186.90 ± 47.21 and 190.60 ± 40.94 ng/ml, 1303.04 ± 234.28 and 1267.78 ± 217.07 ng·hour/ml, and 1328.08 ± 243.84 and 1293.22 ± 224.82 ng·hour/ml under fasting condition, and 151.55 ± 23.86 and 154.08 ± 30.40 ng/ml, 1215.65 ± 197.62 and 1199.26 ± 186.23 ng·hour/ml, and 1241.76 ± 202.47 and 1225.54 ± 192.10 ng·hour/ml under fed condition, respectively. CONCLUSIONS: The two formulations of empagliflozin were bioequivalent, and both were generally well tolerated under fasting and fed conditions.