BIOEQUIVALENCE STUDY BETWEEN TWO FORMULATIONS OF TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN COATED TABLETS IN HEALTHY MALE AND FEMALE SUBJECTS UNDER FASTING CONDITIONS

Objective:To evaluate bioequivalence between a new formulation of Tramadol Hydrochloride/Acetaminophen and Ultracet® coated tablets in healthy subjects under fasting conditions.

Methods:The present study was conducted as an open-label, monocentric, randomized, 2 x 2 crossover study on 40 healthy subjects in a state of fasting. The objective of the study was to compare the pharmacokinetic profiles of two formulations of tramadol hydrochloride and acetaminophen-coated tablets. The concentrations of the analytes in human plasma were measured using a validated UPLC-MS/MS method.

Results:The geometric mean of the test/reference ratio, confidence intervals, and power of the test for the pharmacokinetic parametersCmax and AUC0-t, were determined by statistical analysis, in accordance with the Anvisas guidelines. The geometric mean ratio (90% CI) of the test drug/reference drug for acetaminophen was found to be 82.69% to 100.00% for Cmax and 95.36% to 100.34% for AUC0-t. The results for tramadol hydrochloride were 89.01% to 99.25% for Cmax and 94.86% to 100.71% for AUC0-t. The power of the test was greater than 98%.

Conclusion:Both formulations demonstrated bioequivalent profiles, indicating that they are interchangeable in accordance with the Brazilian criteria. This is evidenced by the fact that the confidence intervals for Cmax and AUC0-t ratios were within 80% and 125%, respectively, as stipulated in Anvisa resolution RE nº 1170/2006.