Subject(s)
Ascorbic Acid/metabolism , Glycerol/metabolism , Animals , Drug Combinations , Kinetics , Male , RabbitsABSTRACT
The metabolic pathway of Pinazepam and Diazepam in vitro was studied with rat, guinea pig and dog liver microsomes using a chromatographic and spectrophotometric technique. Two main pathways were observed, N1-dealkylation and C3-hydroxylation. N1-dealkylation was shown to be the predominant reaction for Pinazepam in all the animal species studied, while C3-hydroxylation was the major metabolic pathway for Diazepam in the rat. No oxazepam was found when Pinazepam and Diazepam were incubated with liver microsomes.
Subject(s)
Anti-Anxiety Agents/metabolism , Diazepam/metabolism , Microsomes, Liver/metabolism , Animals , Drug Synergism , Glucosephosphate Dehydrogenase/metabolism , Guinea Pigs , Male , Microsomes, Liver/enzymology , Rats , Species SpecificityABSTRACT
A sensitive and specific assay, involving electron capture gas-liquid chromatography, has been developed for the identification of pinazepam and its metabolites in serum, urine and brain samples from dogs and rats after single or repeated oral administration of the drug. Serum and urine samples from healthy humans after a single oral administration have also been analysed. The identity of gas-liquid chromatographic peaks has been established by mass spectrometry. In blood serum and brain, only pinazepam and its N-depropargylated product (demethyldiazepam) were found; from urine, 3-hydroxypinazepam and oxazepam were also recovered. The sensitivity of the gas-liquid chromatographic method is of the order of 5-10 ng of pinazepam and 15-20 ng of the other three benzodiazepines per ml of serum.
