Safety, Tolerability, and Pharmacokinetics of Voriconazole for Injection in Two Preparations in Chinese Healthy Adult Volunteers

Abstract Voriconazole is a second‐generation, synthetic, triazole antifungal drug based on the structure of fluconazole. We compared the safety, tolerability, and pharmacokinetic characteristics of voriconazole for injection (200 mg) manufactured by at a dose of 6 mg/kg in Chinese healthy adult volunteers. This was a single‐center, randomized, open, 2‐preparation, single‐dose, 2‐period, 2‐sequence, crossover bioequivalence clinical trial. Twenty‐four eligible, healthy, male, and female volunteers were assigned randomly to one of 2 dose‐sequence groups (test‐reference group or reference‐test group) in a 1:1 block. The voriconazole concentration in plasma was determined by protein precipitation and high‐performance liquid chromatography‐tandem mass spectrometry. The main PK parameters were calculated on the basis of a noncompartmental model. The ratio of the geometric mean of the maximum plasma drug concentration, area under the plasma concentration–time curve from time 0 to the last time of quantifiable concentration, and area under the plasma concentration‐time curve from time 0 to infinity of the test preparation, and the reference preparation was 100.4%, 102%, and 102.2%, respectively. The 90% confidence intervals were between 80% and 125%, indicating that the 2 preparations were bioequivalent. The adverse events experienced by healthy adult volunteers were mild. Both preparations had a good safety profile.