Synthesis and profiling of [3H]trantinterol excretion following oral administration of rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To synthesize[3H]labelled trantinterol and determine the mass balance in rats and the profile of trantinterol and its metabolites in excreta. METHODS [3H]Trantinterol was synthesised from the intermediate1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-bromo-ethanone through reduction by sodium borotritide and aminolysis by t-butylamine. Following an oral dose of[3H] trantinterol(45.5 MBq·kg-1)to bile duct cannulated(BDC)rats and normal rats. Bile,urine and faeces were collected individually before and after dosing at different times. Liquid scintillation counter(LSC) was used to detect total radioactivity recovery and HPLC/radio-detector for metabolite profiling in urine and bile. RESULTS The majority(73.6%)of the administered radioactivity was recovered in the first 24 h postdose with 48.3%in urine and 25.4%in faeces. It was cumulated to(84.7±6.8)%till 168 h. In BDC rats,29.3%of the dose was recovered in the bile 3 d post-dose. According to the peak area ratio determined by HPLC/radio-detector,only 4.7%and 9.5%of the radioactive dose were excreted as the parent drug in urine and bile,respectively,while the majority of the remaining radioactivity was excreted in the form of various metabolites. CONCLUSION Following oral administration in rats,trantinterol is completely absorbed,extensively metabolized and rapidly excreted mainly in urine as various metabolites.