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

Document Type

Article

Publication Date

1-1-2007

Description

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 AUCt, AUCinfinity, Cmax, Tmax, T1/2, and Ke) were determined from the plasma concentrations of nor-TMB of both formulations. AUCt, AUCinfinity, and Cmax 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 AUCt; 98.60%-113.20% for AUCinfinity; 90.85%-107.87% for Cmax) 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.

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