Bioequivalence study of two fluconazole capsule formulations in healthy volunteers.
OBJECTIVE
To compare the bioavailability of a fluconazole 150 mg capsule formulation from Laboratório Teuto Brasileiro Ltd., Brazil (test formulation), and Zoltec 150 mg capsule from Laboratórios Pfizer Ltd., Brazil (reference formulation), in 24 volunteers of both sexes.


METHODS
The study was conducted open with randomized 2-period crossover design and a 2-week washout period. Plasma samples were obtained over a 168-hour interval. Fluconazole concentrations were analyzed by combined reversed-phase liquid chromatography and tandem mass spectrometry (LC/MS/MS) with positive ion electrospray ionization using selected ion monitoring method. From the fluconazole plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C(max).


RESULTS
Geometric mean of fluconazole/Zoltec 150 mg individual percent ratio was 102.6% for AUC(last), 102.2% for AUC(0-inf) and 109.4% for C(max). The 90% confidence intervals were 97.3-108.2%, 97.0-107.8%, and 103.1-116.0%, respectively.


CONCLUSIONS
Since the 90% CI for both Cmax, AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that fluconazole 150 mg capsule was bioequivalent to Zoltec 150 mg, according to both the rate and extent of absorption.
Pereira
R
R
Synchrophar Assessoria e Desenvolvimento de Projetos Clinicos, Campinas, Brazil.
Fidelis
S
S
Vanunci
M L P
ML
Oliveira
C H
CH
Mendes
G D
GD
Abib
E
E
Moreno
R A
RA
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001938:Brazil; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization; D013810:Therapeutic Equivalency
D002214:Capsules; D015725:Fluconazole