METABOLISM AND EXCRETION OF A 3-PROPYLOXY-1,4-BENZODIAZEPINE DERIVATIVE AFTER SINGLE AND COURSE ADMINISTRATIONS

The aim of the work was studying of excretion ways and their effectiveness after oral propoxazepam administration single and after its non-radioactive analog administration course. Excretion parameters of 214C-7-bromo-5-(o-chlorophenyl)-3-propoxy-1,2-dihydro-3H-1,4-benzodiazepine-2-one (propoxazepam) were determined after single administration and after previous course (7 days, 35.2 mg/kg) administration of non-radioactive analog by liquid scintillation photometry. Metabolites identification was performed on a HPLC-mass chromatograph with 1260 Infinity 6530 Accurate Mass Q-TOF detector (Agilent Technologies, USA). It was found that after a single administration propoxazepam is slowly excreted from the body (kel=(0.019±0.050) h-1), mainly with the urine ((67.5±18.5)% of the administered dose). Long term (7 days) propoxazepam administration did not change its excretion parameters (kel after previous course administration was (0.016±0.007) h-1), and has little effect on the redistribution of radioactive material quantity excreted. During propoxazepam metabolism in mice hydroxylation at aromatic ring with further methylation as well as 3-hydroxyderivative formation occurs, which proves the partial alcoxypart elimination from the parent molecule.