Comparative Bioavailability of Two Estazolam Tablet Formulations in Indonesian Healthy Volunteers

Abstract

Aim:

To compare the bioavailability of two estazolam (CAS 29975-16-4) tablet formulations (Estalin® 2 mg tablets as test formulation and 2 mg tablets of the originator product as reference formulation).

Methods:

The study was conducted according to an open label, randomized two-way cross-over design with a two-week washout period. Twenty-four subjects received each of the two estazolam formulations. Blood samples for pharmacokinetic profiling were taken up to 72 h after drug administration in fasting condition. Plasma concentrations of estazolam were determined with a validated HPLC method with ultraviolet detection. Pharmacokinetic parameters were calculated from observed plasma concentration-time profiles.

Results:

The mean AUC_0–t, AUC_0–∞ and C_max were 2581.38 ng • h/mL, 2934.37 ng • h/mL and 95.25 ng/mL, respectively for the test formulation and 2835.75 ng • h/mL, 3207.73 ng • h/mL and 99.32 ng/mL, respectively, for the reference formulation. The median T_max for both formulations was 1 h. The point estimates and 90% confidence intervals for AUC_0–t, AUC_0–∞ and C_max were 91.03% (87.48–94.72%), 91.48% (86.67–96.55%) and 95.90% (92.60–99.31%) respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines.

Conclusion:

These results indicate that two formulations of estazolam are bioequivalent and, thus, may be prescribed interchangeably.

Key words

Benzodiazepines - CAS 29975-16-4, - Estalin® - Estazolam, bioequivalence, pharmacokinetics - Hypnotics - Sedatives

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