Bioequivalence Study of Two Minocycline Capsule Formulations in Healthy Volunteers

Abstract

The bioequivalence of two capsule formulations containing 100 mg minocycline was assessed in 12 healthy adult male and female volunteers in a crossover, randomized, single-blind study. The participating volunteers were required to fast overnight and in the next morning and were given orally one capsule of the test drug (Acnez®) or one capsule of the reference drug. Blood samples were drawn immediately before taking the drug (control), and at 0.33, 0.67, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 h after drug administration. One week after the first drug administration (washout period), the procedure was repeated using the alternate drug.

Plasma concentrations of the drug were determined by high performance liquid chromatography method with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 60 h (AUC_t), area under the plasma concentration-time curve from time zero to infinity (AUC_inf), the peak plasma concentration of the drug (C_max), time needed to achieve the peak plasma concentration (t_max), and the elimination half life (t_1/2).

The mean AUC_t, AUC_inf, C_max, and t were 18 038.55 ng · h · mL⁻¹, 19 648.21 ng · h · mL⁻¹, 1 076.01 ng · mL⁻¹, and 17.33 h, respectively, for the test drug and 17 979.43 ng · h · mL⁻¹, 19 639.78 ng · h · mL⁻¹, 1 095.97 ng · mL¹, and 16.44 h, respectively, for the reference drug. The median (range) of t_max of the test drug and reference drug were 2.0 (1.0 – 4.0) h and 2.0 (0.67 – 4.0) h, respectively.

The geometric mean ratios of the test drug/the reference drug for AUC_t, AUC_int, and C_max were 98.27% 98.30%, and 97.31%, respectively. The 90% confidence intervals (CIs) were 89.26–108.19% for AUC_t, 89.95–107.41% for AUC_inf, and 89.55–105.73% for C_max. Using Wilcoxon matched-pairs test on the original data, there was no statistically significant difference found between the test and the reference drug products for t_max values.

It can be concluded that the two minocycline capsules (test drug and reference drug) are bioequivalent in terms of the rate and extent of absorption.

Key words

Acnez® - Tetracycline antibiotics - CAS 13614-98-7 - Minocycline, bioavailability, bioequivalence, pharmacokinetics

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