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Studies on the pharmacokinetics and metabolism of N4-carbamoyl-1,3,4,5-dihydro-diazepam (Uxepam®) in rats, dogs and man

✍ Scribed by M. Vajda; Zs. Tegyey; M. Kozma; L. Vereczkey

Publisher
Elsevier Science
Year
1986
Tongue
English
Weight
461 KB
Volume
4
Category
Article
ISSN
0731-7085

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✦ Synopsis

The pharmacokinetics and metabolism of Uxepams', a new minor tranquillizer, have been investigated in rats [2], dogs and man. For the experiments in rats [2] separation of metabolites of 2-14C-uxepam was achieved by thin-layer chromatography.

In the experiments on dogs and man, Extrelut microcolumns were used for preseparation. Recovery was 95% f 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-'. The metabolites 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.

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