It has been reported that voriconazole is used to treat infections caused by invasive aspergillosis, fluconazole-resistant Candida, Actinoplanes and Fusarium. This study was performed to investigate the safety of prodrug of voriconazole (POV) and explore the distribution and metabolism of POV in vivo. The POV for injection was formulated into POV injection. In this study, POV injection was given intravenously at the doses of 0, 30, 60, and 120 mg/kg/d to SD rats for 4 weeks consecutively. Toxicokinetic study was also performed to explore its distribution and metabolism. POV injection was found to be safe and well tolerated. Some statistically significant differences in relative liver weight were observed and several cases of hepatocyte hypertrophy occurred after the 4-week POV injection treatment. Liver-related toxic response could be reversed after recovery period. The results of toxicokinetics showed that POV can rapidly converts to voriconazole in SD rats after administration. The exposure of voriconazole in each group was significantly different between male and female rats. The results showed that the target organ for the toxic effect of POV is liver and the no-toxic-reaction-dose for long-term administration of POV injection was 60 mg/kg/d.
Keywords: One-month toxicity study; POV; Toxicokinetic; Voriconazole.
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