Evaluation of Pharmacokinetics and Safety With Bioequivalence of Voriconazole Injection of 2 Formulations in Chinese Healthy Volunteers: Bioequivalence Study

Abstract

AbstractVoriconazole is a first‐line medicine for treating invasive aspergillosis. We aimed to evaluate the bioequivalence (BE) of voriconazole injection in Chinese healthy volunteers (HVs). In this single‐center, randomized, single‐dose, 2‐cycle, fasting‐dose BE study, HVs (n = 24) were 1:1 divided into 2 groups (test [T]–reference [R] and R–T) and received 6 mg/kg of voriconazole intravenously with a 7‐day washout. The plasma was collected for up to 72 hours at the time point after dosing on day 1/day 8. The plasma concentration of voriconazole was measured by liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were ascertained on the basis of a noncompartmental model. In the BE study, the geometric mean ratios of the maximum concentration, area under the concentration–time curve from time 0 to the last measurable plasma concentration, and area under the concentration–time curve from time 0 to infinity were 101.1%, 105.6%, and 105.5%, respectively, and the 90%CI fell within 80%–125%. Adverse events were observed in 26.1% of subjects in the T formulation stage and 17.4% in the R formulation stage. Under the BE study, voriconazole values from T and R formulations were bioequivalent.