Studies on the pharmacokinetics and metabolism of N(4)-carbamoyl-1,3,4,5-dihydro-diazepam (Uxepam(R)) in rats, dogs and man.
The pharmacokinetics and metabolism of Uxepam(R), a new minor tranquillizer, have been investigated in rats [2], dogs and man. For the experiments in rats [2] separation of metabolites of 2-(14)C-uxepam was achieved by thin-layer chromatography. In the experiments on dogs and man, Extrelut microcolumns were used for preseparation. Recovery was 95% +/- 12.77 (S.D.) determined by radioactive tracer experiments. The compounds were separated and determined by reversed-phase HPLC with UV detection at 240 nm. The limit of detection for uxepam was 10 ng ml(-1). The metabolises were identified by mass spectrometry. The main metabolites in the rat were desmethyl-uxepam, 5-hydroxy-phenyl-desmethyl-uxepam and diazepam. Desmethyl-carbamoyl-dihydro-diazepam, diazepam and desmethyl-diazepam were found in human plasma. In dogs only one metabolite, desmethyl-uxepam, was detected in plasma. Enterohepatic recycling was observed in dogs and in humans.
Vajda
M
M
Central Research Institute for Chemistry, Budapest, Hungary.
Tegyey
Z
Z
Kozma
M
M
Vereczkey
L
L