Average bioequivalence of two oral formulations of fluconazole in healthy subjects after multiple dosing.
OBJECTIVE
To assess the average bioequivalence of two oral dosage forms of fluconazole--test (Fungolon, Antibiotic Co.) and reference (Diflucan, Pfizer)--in 18 healthy volunteers in a multiple dose-balanced, two-period, crossover study design.


METHODS
The dosage regimen consisted of seven days treatment (first day 100 mg and 50 mg thereafter for six days given orally) and a washout period of two weeks between different treatments. Plasma samples were taken at regular time intervals according to the study protocol for measuring of plasma fluconazole concentrations. The primary and secondary parameters AUC(168-192), Cav, %PTF, Cmax, %Swing, %AUCF, 100 Cmax/AUC, T above Cav, and Tmax were estimated.


RESULTS
The point estimates--geometric means of the ratios test (T)/reference (R) and the 90% confidence intervals (CI) for the ratios of expected medians (T)/(R), assuming a multiplicative model, estimated by parametric and nonparametric analysis--were in the defined ranges for accepting of bioequivalence for two of the primary metrics. The point estimates and the 90% CIs after parametric analysis of AUC(168-192) were 1.00 (0.98-1.02) and for the metric %PTF exceeded the accepted range for bioequivalence after parametric analysis the point estimate and 90% CI were 0.93 and (0.799-1.08).


CONCLUSIONS
The two preparations were considered to be bioequivalent in the rate and extent of absorption with significant variability across subjects.
Chemical Pharmaceutical Research Institute, NIHFI, Sofia, Bulgaria.
I
I
Atanasova
K
K
Bozhinova
D
D
Terziivanov
D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013810:Therapeutic Equivalency
D000935:Antifungal Agents; D015725:Fluconazole