Pharmacokinetics of mirabegron sustained-release tablets in beagle dogs / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a simple, sensitive method of liquid chromatographic-tandem mass spectrometric (LC-MS/MS) for determination of mirabegron in dog plasma, and to evaluate the pharmacokinetics for single dose of different formulations of mirabegron sustained-release tablets in dogs. METHODS: The analyte mirabegron and internal standards (IS) tolbutamide were separated on a BEH C18 column (2.1 mm×50 mm, 1.7 μm) with mobile phase of 0.1% formic acid water solution-0.1% formic acid methyl cyanides solution using a gradient elution mode at a flow rate of 450 μL·min-1. In accordance with randomized two-period self crossover study, eight dogs were given single oral dose of the test preparation and reference preparation, then the concentration of mirabegron in plasma was determined, the pharmacokinetic parameters were calculated and the difference of the two preparations were evaluated. RESULTS: The linear range of mirabegron in Beagle dogs plasma was 1-1000 ng·mL-1. The accuracy and the precisions of intra-day and inter-day also were qualified. After a single dose administration of the test preparation and reference preparation, the pharmacokinetic parameters were as follow t1/2 were (7.14±1.59) vs (7.13±1.78) h, pmax were (144.4±77.5) vs (130.3±39.2) ng·mL-1, tmax were (3.72±1.87) vs (4.64±1.55)h, AUC0→8 were (1021±439) vs (989±299)ng·h·mL-1, AUC0→∞ were (1043±441) vs (1010±301)ng·h·mL-1. CONCLUSION: The LC-MS/MS method is suitable for pharmacokinetic study of mirabegron. Moreover, there is no significant difference in the pharmacokinetic profiles between the two preparations of mirabegron.