Bioequivalence of zolpidem hemitartrate: new formulations of 5 mg SL, 10 mg and 12.5 mg XR and comparison of their bioavailabilities

Abstract

Objective: To evaluate pharmaceutical bioequivalence between two formulations of 5 mg zolpidem hemitartrate sublingual and, 10 and 12.5 mg extended-release formulations tablets in healthy subjects under fasting and fed conditions. Methods: An open label, monocentric, randomized, 2 x 2 crossover study in 40 healthy adults under fasting conditions comparing two formulations of zolpidem 5mg sublingual tablets. Analyte concentrations in human plasma were determined using a validated liquid chromatography with a tandem mass spectrometer detector method (LC-MS/MS). The same design was utilized to evaluate the other formulations.
 Results: Statistical analysis has determined geometric mean of test / reference ratio, confidence intervals, and power of the test to the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞. The geometric mean ratio (90%CI) of the test drug/reference drug for zolpidem 5mg were 99.89 to 113.57% for Cmax, 97.15% to 108.40% for AUC0-t, and 97.22% to 108.13% for AUC0-∞. Power of the test was 99.35% for Cmax and 100% AUC0-t, and AUC0-∞. Conclusion: Both test and reference are bioequivalent for all formulations and, therefore, they are interchangeable, according to the Brazilian criteria (Anvisa resolution RE nº 1170/2006), since confidence intervals for Cmax and AUC0-t ratios were within 80% and 125%.