Comparative Bioequivalence Study of Two Marketed Formulation of Betamethasone Injectable Suspensions

Abstract

Background:

The aim of this study was to determine the bioequivalence of generic (test) and branded (reference) formulations of betamethasone injectable suspension in healthy Iranian subjects for the purpose of meeting regulatory requirements for bioequivalence of the generic formulation in Iran.

Methods:

24 healthy Iranian male volunteers were participated for this single-dose, randomized, open label, 2 period crossover study separated by a 2-week washout period. For the assessment of betamethasone, blood samples were obtained before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after drug administration. Plasma concentration of betamethasone was analyzed with a simple, rapid and validated high performance liquid chromatography method with ultraviolet detection. Pharmacokinetic parameters, representing the rate (C_max, T_max), and the extent (AUC_0–t and AUC_0–∞) of betamethasone absorption were calculated and analyzed for 2 formulations. The 2 formulations were to be considered bioequivalent if the 90% confidence intervals (CI)s for the logarithm-transformed values of C_max, AUC_0–t and AUC_0–∞ fell within the predetermined range of 80–125%.

Results:

The 90% CIs of C_max, AUC_0–t and AUC_0–∞ were 85.4–104.4%, 96.2–112.1% and 98.3–115.8%, respectively.

Conclusion:

Based on the 90% CIs of C_max, AUC_0–t and AUC_0–∞ in these healthy Iranian male subjects, the test and reference formulations of betamethasone injectable suspension met the regulatory requirements for bioequivalence.

Key words

bioequivalence - betamethasone injectable suspension - pharmacokinetics - HPLC

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