Comparison of the pharmacokinetics of fosfluconazole and fluconazole after single intravenous administration of fosfluconazole in healthy Japanese and Caucasian volunteers.
OBJECTIVE
To investigate the bioavailability of fluconazole (FLCZ) from fosfluconazole (phosphate pro-drug of FLCZ) and to compare the pharmacokinetics of fosfluconazole and FLCZ in Japanese and Caucasian subjects.


METHODS
In a randomised, double-blind, double-dummy, single-dose, two-period, crossover study, 12 Japanese and 12 Caucasian healthy subjects received a bolus intravenous injection of 1000 mg fosfluconazole or an intravenous infusion of 800 mg FLCZ in random order. Concentrations of fosfluconazole and FLCZ were determined in plasma and urine samples taken up to 144 h and 48 h post-dose, respectively.


RESULTS
The bioavailability of FLCZ after administration of fosfluconazole was 95.2% (95% confidence interval: 89.0, 102.0) in Japanese subjects and 100.6% (94.0, 107.7) in Caucasian subjects. The ratio of bioavailabilities (Japanese/Caucasian) was 94.7% (86.0, 104.3). There were no statistically significant differences in the pharmacokinetic parameters of fosfluconazole (except for AUC(inf)) and FLCZ between Japanese and Caucasian subjects. Although mean AUC(inf) of fosfluconazole was 25.6% (5.6, 49.2) greater in Japanese subjects, the lack of a statistically significant difference in weight-adjusted CL of fosfluconazole demonstrates that the difference in AUC(inf) was due to a difference in body weight. The adverse-event profile was similar in Japanese and Caucasian subjects after both fosfluconazole and FLCZ dosing, and both treatments were well tolerated in each group.


CONCLUSIONS
The pharmacokinetics of fosfluconazole and FLCZ were similar in Japanese and Caucasian subjects. Fosfluconazole is almost completely converted to FLCZ and similar systemic exposure to FLCZ is achieved after single doses of fosfluconazole in both Japanese and Caucasian subjects.
Sobue
Satoshi
S
Pfizer Global R and D, Tokyo Laboratories, Pfizer Japan Inc., Shinjuku Bunka Quint Building 3-22-7, Yoyogi, Shibuya-ku, 151-8589 Tokyo, Japan. Satoshi.Sobue@japan.pfizer.com
Tan
Keith
K
Shaw
Linda
L
Layton
Gary
G
Hust
Rita
R
D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007564:Japan / Q000208:ethnology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010755:Organophosphates / Q000009:adverse effects / Q000493:pharmacokinetics*; D044465:White People
D000935:Antifungal Agents; D010755:Organophosphates; C486878:fosfluconazole; D015725:Fluconazole