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Pharmacokinetics and Safety of Fosfluconazole after Single Intravenous Bolus Injection in Healthy Male Japanese Volunteers
Author(s) -
Sobue Satoshi,
Sekiguchi Kaneo,
Shimatani Katsuyoshi,
Tan Keith
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270003262799
Subject(s) - pharmacokinetics , tolerability , volume of distribution , pharmacology , crossover study , medicine , bolus (digestion) , placebo , adverse effect , anesthesia , alternative medicine , pathology
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.