Comparative Bioavailability Study of Fluconazole Formulation

Fluconazole 제제의 생체이용률 비교시험

Background: This study was conducted to evaluate the bioavailability of Fluconazole formulation in healthy Korean volunteers. Furthermore, the bioequivalence of $Flukan^{\circledR}$ capsule, a fluconazole preparation from Korea United Pharm, Inc., was determined. Methods: The study employed a randomized, two-way crossover Latin square design with a two-week washout period. The test product was $Flukan^{\circledR}$ capsule (Korea United Pharm Inc., South Korea) and the reference was $Diflucan^{\circledR}$ capsule (Pfizer Inc.). The two products were administered in 150 mg single oral doses into 26 healthy Korean volunteers. Serial blood samples were collected for a period of 120 hours. Plasma fluconazole concentrations of the two brands were measured by HPLC using UV detector, and the pharmacokinetic parameters including $AUC_t,\;C_{max},\;T_{max}$, and half-life were determined from plasma concentrations of both formulations. Results: Both formulations were well tolerated in 26 volunteers. Mean $AUC_t,\;C_{max}$ of $Flukan^{\circledR}$ capsule were 1.068 $(90%\;confidence\;interval:\;1.0057{\leq\delta\leq}1.1349)$ and 1.017 $(90%\;confidence\;interval:\;0.9633{\leq\delta\leq}1.0749)$ compared to those of $Diflucan^{\circledR}$ capsule. Mean half-life of $Flukan^{\circledR}$ capsule was $30.41{\pm}5.44$ and that of $Diflucan^{\circledR}$ capsule was $30.74{\pm}5.86$ hr. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were above 90%. The pharmacokinetic parameters $(AUC_t,\;C_{max},\;T_{ max})$ were analyzed statistically with K-BE test 2002 (KFDA). Conclusion : No significant differences between two formulations were observed in terms of $AUC_t\;and\;C_{max}$, the main pharmacokinetic parameters used for bioequivalence evaluation. The results satisfied the bioequivalence criteria of KFDA guidelines, and $Flukan^{\circledR}$ capsule was determined to be bioequivalent to $Diflucan^{\circledR}$ capsule.