Pharmacokinetics and safety of Fosfluconazole after single intravenous bolus injection in healthy male Japanese volunteers.

This was a single blind, placebo-controlled, escalating single-dose, three-period crossover study using two subject cohorts to investigate the safety, tolerability, and pharmacokinetics in healthy male Japanese subjects after intravenous bolus injection of fosfluconazole 50 to 2000 mg, a phosphate prodrug of fluconazole (FLCZ). Fosfluconazole was rapidly converted to FLCZ with only minor amounts excreted in the urine (less than 4% of the dose). Fosfluconazole had a volume of distribution at the higher doses, which was similar to the extracellular volume in man (0.2 L/kg) and was eliminated with a terminal half-life of 1.5 to 2.5 hours. There was apparent dose proportionality in FLCZ pharmacokinetics. C(max) and AUC of FLCZ appeared to increase proportionally with increasing doses of fosfluconazole. There were no apparent dose-dependent trends in t(max), t(1/2), or mean residence time (MRT) of FLCZ. Bolus injection of fosfluconazole was well tolerated at doses of up to 2000 mg in healthy Japanese subjects.