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Ketorolac Tromethamine Sublingual Tablet: A Randomized, Single-Dose, Two-Sequence, Two-Period, Crossover Study to Assess the Bioequivalence between Two Formulations

Jessica Meulman, Marcelo Gomes Davanco, Fernando Costa, Fernando Bastos Canton Pacheco, Kadmiel Vinicio Santos Teixeira, Silvana Aparecida Calafatti Carandina, Celso Francisco Pimentel Vespasiano

Ketorolac Tromethamine is a non-hormonal anti-inflammatory drug, with potent analgesic action, used to short- term treatment of moderate to severe acute pain. In order to register a generic product in Brazil, it was performed a bioequivalence study under fasting conditions between two ketorolac tromethamine sublingual tablets. The study was designed and conducted in accordance with ethical principles and current legislation, presenting an open, randomized, with two treatments, two periods and two sequences crossover design. For this study, 32 healthy men and women were selected; however, 30 participants completed the study. Blood samples were collected serially up to 24 h post-drug administration and plasma concentrations of ketorolac were obtained by a validated bioanalytical method, using ketorolac-d5 as an internal standard. A non-compartmental model was used to determine the pharmacokinetic parameters. Bioequivalence between test and reference formulation was demonstrated by constructing the 90% confidence intervals calculated for the corresponding ratios of the transformed data of the pharmacokinetic parameters C_max , AUC_0-t and AUC_0-inf . The point estimates and 90% confidence intervals obtained were 101.195 (96.12%-106.53%), 99.43% (95.27%-103.78%) and 98.93% (94.86%-103.16%), respectively. Considering these values are within the range of 80% to 125%, it is possible to conclude that the two formulations are bioequivalent in terms rate and extent of absorption and, therefore, are interchangeable. Both formulations showed to be safe and well tolerated.