Pharmacokinetic and bioequivalence evaluation of two formulations of 100 mg trimebutine maleate (Recutin™ and Polybutin™) in healthy male volunteers using the LC–MS/MS method

Abstract

Background Trimebutine maleate is a prokinetic agent that acts directly on the smooth muscle of the GI tract. A bioequivalence (BE) study of 2 oral formulations of 100 mg trimebutine maleate (TMB) was carried out in 24 healthy male Korean volunteers according to a crossover–randomized design. Methods Subjects were given a single dose of 2 100 mg tablets of each formulation. The test and reference formulations were Recutin™ (Hutax Co., South Korea) and Polybutin™ (Samil Co., South Korea), respectively. Each set of tablets was administered with 240 ml of water to subjects after 10 h overnight fasting on 2 treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 36 h. Plasma was analyzed for the main metabolite of TMB, N-monodesmethyl trimebutine (nor-TMB), by a validated LC with MS/MS detection capacity for nor-TMB in the range 5–1500 ng/ml, with a lower limit of quantification (LLOQ) of 5 ng/ml. Several pharmacokinetic (PK) parameters (including AUC t, AUC infinity, C max, T max, T 1/2, and K e ) were determined from the plasma concentrations of nor-TMB of both formulations. AUC t, AUC infinity, and C max were tested for BE after log-transformation of the data. Results No significant difference was found based on ANOVA; 90% confidence intervals (98.98%112.03% for AUC t; 98.60%–113.20% for AUC infinity; 90.85%–107.87% for C max) for the test and reference were found within KFDA acceptance range of 80–125%. Conclusions Based on these statistical inferences, it was concluded that Recutin™ is bioequivalent to Polybutin™ and can be used interchangeably in a clinical setting.