Truncated AUC in the evaluation of fluconazole bioequivalence. A cross-over, randomised, open-label study in healthy volunteers.
The bioequivalence of two capsule formulations (test and reference) containing 200 mg fluconazole (CAS 86386-73-4) was assessed in 24 healthy volunteers in an open, randomised, crossover, 2 periods x 2 sequences single dose study with a minimum washout period of 14 days. Plasma samples were obtained over 168 h (at baseline, 1 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 120 h and 168 h after administration) and fluconazole concentrations were determined by means of an HPLC-WV method (limit of quantification: 0.2 microg/mL). Pharmacokinetic parameters used for bioequivalence assessment (AUClast, AUCinf and Cmax) were determined from the fluconazole concentration data using non-compartmental analysis. The results showed that all 90% confidence intervals (obtained by ANOVA) were 100.89-110.24 for Cmax, 99.07-107.35 for AUClast and 95.42-105.17 for AUCinf, that is, all within the predefined ranges. Furthermore AUCs truncated at 24, 48, 72 and 120 h were also within the 80-125% range. It may be therefore concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.
Portolés
Antonio
A
Servicio de Farmacología Clínica, Hospital Clínico San Carlos, Madrid, Spain. aportoles.hcsc@salud.madrid.org
Almeida
Susana
S
Terleira
Ana
A
de Pablo
Itziar
I
Filipe
Augusto
A
Cruz Caturla
Maria
M
Moreno
Alfonso
A
D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency
D000935:Antifungal Agents; D015725:Fluconazole