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Bioequivalence of Two Oral Fluconazole Formulations in Healthy Subjects: a Single Dose, Open-Label, Randomized, Two-Period Crossover Study

Author(s): Jose Antonio Palma-Aguirre | Mireya Lopez-Gamboa | Teresita de Jesus Castro-Sandoval | Roxana Hernández-González | Julian Mejía-Callejas

Journal: Journal of Bioequivalence & Bioavailability
ISSN 0975-0851

Volume: 02;
Issue: 02;
Start page: 023;
Date: 2010;
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Keywords: Fluconazole | Pharmacokinetics | Bioequivalence | Bioavailability | HPLC

Background: Fluconazole is a triazole antifungal agentlabeled for use in the treatment of oropharyngeal and esophagealcandidiasis and cryptococcal meningitis, marketedin Mexico in several generic trade names.Objective: The aim of this study was to compare thebioavailability and determine the bioequivalence of one testformulation (fluconazole oral tablet) with its correspondinglist reference-drug formulation in Mexico (a list issuedby Mexican Health Authorities).Methods: A single dose, randomized, open-label, 2-periodcrossover, postmarketing study was conducted. Eligiblesubjects was selected comprising healthy Mexicanadults of either sex, and subjects were randomly assignedto receive 1 test formulation of fluconazole followed bythe corresponding reference drug formulation, or viceversa,with a 1-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single capsule offluconazole 150 mg tablet formulation. For the analysis ofbioequivalence, including Cmax, AUC from time 0 (baseline)to time t (AUC0-t), and AUC from baseline to infinity(AUC0-¥), blood samples were collected at baseline, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72 and 96 hours afterdosing. The formulation was considered bioequivalent ifthe geometric mean ratios (test/reference) of the Cmax andAUC were within the predetermined range of 80% to125%. Tolerability was determined by clinical assessment,monitoring vital signs, laboratory analysis results, and subjectinterviews regarding adverse events.Results: A total of 24 subjects were enrolled in the studyThe bioequivalence test drug values were Cmax of 4.44 ±0.79 μg/mL, tmax of 2.59 ± 1.03 h, AUC0-t of 152.21 ± 28.89h. μg/mL, AUC0-¥ of 175.13 ± 48.98 h. μg/mL, and referencedrug values of Cmax of 4.38 ± 0.83 μg/mL, tmax of 2.70± 1.15 h, AUC0-t of 154.67 ± 26.10 r. μg/mL, AUC0-¥ of174.33 ± 31.10 hr. μg/mL.Conclusions: In this study in healthy Mexican adult subjects,a single dose of fluconazole 150 mg of the test formulationwas found to be bioequivalent to the correspondingreference formulation according to the regulatory definitionof bioequivalence based on the rate and extent ofabsorption. Both formulations were generally well tolerated.
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