Comparative Bioavailability of Two Estazolam Tablet Formulations in Indonesian Healthy Volunteers

Aim: To compare the bioavailability of two estazolam (CAS 29975-16-4) tablet formulations (Estalin (R) 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-infinity). 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-infinity) 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.