Comparative Study of the Main Pharmacokinetic Parameters of a Newly Developed Fluconazole Formulationin Healthy Iraqi Volunteers

Abstract

Objective: Crossover design study was carried out to compare the main pharmacokinetic parameters of a newly developed generic formula of fluconazole as a test product with the standard reference fluconazole product of Pfizer company under the brand name Diflucan®.
Subjects and methods: Twenty-eight volunteers of healthy Iraqi male were involved in this study. The formulations were administered as a single 150 mg dose of the tested and reference fluconazole after an overnight fasting state. Plasma concentration of fluconazole from each volunteer were measured over 24-hour interval using high performance liquid chromatography (HPLC) assay. From serum concentration versus time, data of each subject, the pharmacokinetic parameters represented by the mean ± SD maximum concentration (Cmax) of fluconazole, time to reach maximum fluconazole concentration (Tmax), area under the curve (AUC0-t) were calculated.
Results: The mean±SD (% CV) of the Cmax (ng/ml), time to reach T max (h), AUC0-t (ng.h/ml) were 2894.52±558.94 (19.4) and 3144.39±564.82 (17.4), 1.94±0.54 (55.3) and 1.82±0.88 (52.9), 88466.1±17632.4 (20.8) and 92274.5±15324.7 (15.9) for the tested and reference produce, respectively. Ratio of Cmax (ng/ml), time to reach Tmax (h), AUC0-t (ng.h/ml) for the test versus the reference products were 0.92, 0.95 and 1.06, respectively. Since the 90% confidence intervals for these parameters were within the 80-125% of the interval ratio proposed by FDA, it was concluded that the newly developed fluconazole 150 mg tablet was bioequivalent to the reference product produced by Pfizer in term of the rate in addition to the extent of absorption and bioavailability. Consequently, newly developed fluconazole 150 mg tablet is interchangeable with fluconazole 150 mg tablet manufactured by Pfizer and can be prescribed as an alternative in the Iraqi market.