BACKGROUND: Because of its systemic action, fluconazole is prescribed for a variety of fungal infections. However, therapeutic failure might result when a patient is switched between an innovator drug and a nonbioequivalent generic formulation. Pharmacokinetic (PK) studies investigating the bioequivalence of generic and innovator drugs can minimize such risks. OBJECTIVE: The aim of this study was to compare the PK profiles and relative bioavailabilities of 2 oral formulations of fluconazole: Diflucan (reference; Pfizer Corporation Austria GmbH, Wien, Austria) and Funzol (test; Bosnalijek d.d., Pharmaceutical and Chemical Industry, Sarajevo, Bosnia and Herzegovina), both prepared as capsules containing 150 mg of active drug. METHODS: A single oral dose of fluconazole was given under fasting conditions to healthy, white volunteers aged 18 to 55 years in this open-label, randomized, crossover study. A 3-week washout period was applied between each of the 2 doses. Serum samples were obtained before dosing and at various time points after dosing up to 144 hours and were analyzed for fluconazole concentration using a high-performance liquid chromatography-UV method. PK parameters representing the extent (AUC(0-infinity)) and rate (CmaX and T(max)) of absorption of fluconazole were obtained. An analysis of variance, a power analysis, 90% CI, and two 1-sided tests were used for statistical analysis of relative differences between the 2 drugs. Bioequivalence was concluded if the 90% CIs for the geometric mean ratios of AUC(0-infinity) and C(max) were between 0.80 and 1.25. A study investigator monitored the volunteers for adverse effects at 5 defined time points during the clinical part of the investigation. RESULTS:Thirteen men and 11 women (mean age, 33.3 years; mean weight, 73.6 kg) completed the study. The respective point estimates of the ratios of geometric means of log-transformed C(max) and AUC0(0-infinity) of fluconazole (test vs reference) were 0.985 and 1.047, with 90% CIs of 0.894 to 1.085 and 0.927 to 1.182, respectively. Differences in T(max) also did not reach statistical significance. No adverse effects were reported by the subjects or revealed by clinical or laboratory tests. CONCLUSIONS: The study failed to demonstrate any statistically significant differences in C(max) and AUCO(0-infinity) values between the test and reference formulations of oral fluconazole 150 mg in this small, select population of healthy volunteers. On that basis, and according to both the rate and extent of absorption, the test and reference formulations were considered bioequivalent.
RCT Entities:
BACKGROUND: Because of its systemic action, fluconazole is prescribed for a variety of fungal infections. However, therapeutic failure might result when a patient is switched between an innovator drug and a nonbioequivalent generic formulation. Pharmacokinetic (PK) studies investigating the bioequivalence of generic and innovator drugs can minimize such risks. OBJECTIVE: The aim of this study was to compare the PK profiles and relative bioavailabilities of 2 oral formulations of fluconazole: Diflucan (reference; Pfizer Corporation Austria GmbH, Wien, Austria) and Funzol (test; Bosnalijek d.d., Pharmaceutical and Chemical Industry, Sarajevo, Bosnia and Herzegovina), both prepared as capsules containing 150 mg of active drug. METHODS: A single oral dose of fluconazole was given under fasting conditions to healthy, white volunteers aged 18 to 55 years in this open-label, randomized, crossover study. A 3-week washout period was applied between each of the 2 doses. Serum samples were obtained before dosing and at various time points after dosing up to 144 hours and were analyzed for fluconazole concentration using a high-performance liquid chromatography-UV method. PK parameters representing the extent (AUC(0-infinity)) and rate (CmaX and T(max)) of absorption of fluconazole were obtained. An analysis of variance, a power analysis, 90% CI, and two 1-sided tests were used for statistical analysis of relative differences between the 2 drugs. Bioequivalence was concluded if the 90% CIs for the geometric mean ratios of AUC(0-infinity) and C(max) were between 0.80 and 1.25. A study investigator monitored the volunteers for adverse effects at 5 defined time points during the clinical part of the investigation. RESULTS: Thirteen men and 11 women (mean age, 33.3 years; mean weight, 73.6 kg) completed the study. The respective point estimates of the ratios of geometric means of log-transformed C(max) and AUC0(0-infinity) of fluconazole (test vs reference) were 0.985 and 1.047, with 90% CIs of 0.894 to 1.085 and 0.927 to 1.182, respectively. Differences in T(max) also did not reach statistical significance. No adverse effects were reported by the subjects or revealed by clinical or laboratory tests. CONCLUSIONS: The study failed to demonstrate any statistically significant differences in C(max) and AUCO(0-infinity) values between the test and reference formulations of oral fluconazole 150 mg in this small, select population of healthy volunteers. On that basis, and according to both the rate and extent of absorption, the test and reference formulations were considered bioequivalent.