Synthesis and profiling of ”3H”trantinterol excretion following oral administration of rats
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 intermediate 1(4amino3chloro5trifl uoromethylphenyl)2bromoethanone through reduction by sodium borotritide and aminolysis by tbutylamine.Following an oral dose of ”3H” trantinterol (45.5 MBq· kg1)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/radiodetector 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 postdose.According to the peak area ratio determined by HPLC/radiodetector, 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.
tritium labelling trantinterol chemistry techniques synthetic matabolism
ZHANG Tian-hong ZHANG Cheng YANG Cui-ping WANG Xiao-ying LIAO Sha SUN Mu-zhen LI Jing-lai ZHANG Zhen-qing
Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China
国内会议
北京
英文
393-400
2015-11-02（万方平台首次上网日期，不代表论文的发表时间）