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Bioequivalence of Two Oral Ciprofloxacin Formulations

  • Clinical Pharmacokinetic
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Abstract

Objective: To establish bioequivalence between two oral formulations of ciprofloxacin 500mg tablets (reference formulation: Ciproxina®, Bayer Laboratories; test formulation: Cinaflox®, SteinLaboratories)

Design: A phase I crossover, randomised study with a 7-day washout period.

Methods: A single dose of either drug was administered to 18 healthy male and female volunteers. Blood samples were drawn before each administration and on 14 occasions up to 24 hours after drug administration. Quantification of plasma concentrations was done by reverse-phase high performance liquid chromatography (HPLC). The area under the plasma concentration versus time curve for time zero to infinity (AUC∞) was calculated by the trapezoidal method, and maximum concentrations (Cmax) and time to reach Cmax (tmax) were obtained directly from the concentration versus time curves. Cmax/AUC∞ was also calculated. After logarithmic transformation, analysis of variance (ANOVA) was used for statistical analysis of AUC∞, Cmax and Cmax/AUC∞, and tmax was evaluated untransformed using the Mann-Whitney U-test. Classic confidence intervals (CI) and calculation of two one-sided t-tests (Schuirmann) were used as criteria for evaluation of bioequivalence.

Results and Conclusion: There were no gender, administration order or group biases. The mean values of the pharmacokinetic parameters obtained for the reference formulation were AUC∞ = 11.9457mg·h/L, Cmax = 2.1622 mg/L, Cmax/AUC∞ = 0.1837h−1, tmax= 1.55h. For the test formulation, the mean values were AUC∞ = 11.1511mg·h/L, Cmax = 1.9939 mg/L, Cmax/AUC∞ = 0.1824h−l, tmax= 1.6388h. After comparison of these four specific pharmacokinetic parameters for bioequivalence, it was concluded that, according to the recommendations of the 1992 European Guidelines (data transformed logarithmically and AUC∞ in the relationship AUCt/AUC∞ ≥ 80%), the test formulation is bioequivalent in the extent (CI 85.0–104.0) and rate of absorption (CI 85.4–100.6) to the reference formulation. Since the difference between the test and reference means for tmax was 0.07h, and the CI for Cmax/AUG∞ were 89.1 to 109.0, the two formulations are interchangeable. Both formulations were well tolerated; adverse effects reported were not clinically relevant.

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Notes

  1. 1Multisource pharmaceutical products are pharmaceutically equivalent products that may or may not be therapeutically equivalent. Those that are therapeutically equivalent are interchangeable with the innovator product.

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Authors and Affiliations

  1. Department of Pharmacotherapy, CCSS, School of Medicine, University of Costa Rica, 1467-1250, Escazú, San José, Costa Rica

    Maritza Morera, Jaime Cortés & José Moncada

  2. Research and Development Department, Stein Laboratory, Cartago, Costa Rica

    Irina Ramos

  3. School of Pharmacy, University of Costa Rica, San José, Costa Rica

    Lidieth Fonseca

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  1. Maritza Morera
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  2. Jaime Cortés
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  3. Irina Ramos
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  4. José Moncada
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  5. Lidieth Fonseca
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Correspondence to Maritza Morera.

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Morera, M., Cortés, J., Ramos, I. et al. Bioequivalence of Two Oral Ciprofloxacin Formulations. Clin. Drug Investig. 21, 137–145 (2001). https://doi.org/10.2165/00044011-200121020-00006

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