Pharmacokinetic and bioequivalence evaluation of two formulations of 100 mg trimebutine maleate (Recutin (TM) and Polybutin (TM)) 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 (TM) (Hutax Co., South Korea) and Polybutin (TM) (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 I 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,; 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 (TM) is bioequivalent to Polybutin (TM) and can be used interchangeably in a clinical setting.