Pharmacokinetics and bioequivalence of trimebutine dispersive tablet in healthy subjects
Jiang, H.; Ding, L.; Yang, J.; Huang, X.; Liu, G-yu.; Zhang, Z-xing.
Yao Xue Xue Bao 39(3): 208-211
2004
ISSN/ISBN: 0513-4870 PMID: 15171657 Document Number: 577061
Aim: To develop an HPLC-ESI-MS assay for determination of trimebutine in human plasma and to investigate the pharmacokinetics and bioequivalence of two trimebutine tablets in human. Methods: After being made alkaline with saturated sodium bicarbonate, plasma was extracted by cyclohexane and separated by HPLC on a reversed-phase C18 column with a mobile phase of 10 mmolcntdotL-1 ammonium acetate buffer solution (pH 3.5)-methanol (18:82). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 388 for trimebutine and m/z 280 for the internal standard (sibutramine, IS). The fragmentor voltage was 50 V. A randomized cross-over design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer. Results: Calibration curve was linear over the range of 0.3-150 mugcntdotL-1. The main pharmacokinetic parameters of Tin1/2, Tmax and Cmax were (9.2+-2.8) h, (1.0+-0.3)h and (40+-20) mugcntdotL-1 for the reference tablet; (9.2+-2.3)h, (0.9+-0.4) h and (41+-20) mugcntdotL-1 for the test tablet. The relative bioavalability of the test tablet was (97+-13)%. The results of variance analysis and two one-sided t-test showed that there was no significant difference between the two formulations in the AUC and Cmax. Conclusion: The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.