Biotransformation of carbazeran in guinea pig: effect of hydralazine pretreatment

Xenobiotica. 1994 Jan;24(1):37-47. doi: 10.3109/00498259409043219.

Abstract

1. After administration of [14C]-carbazeran by oral gavage to guinea pigs, 48% of the dosed radioactivity was recovered in urine and 46% in faeces after 144 h. 2. The major urinary metabolite was identified by infrared spectroscopy and mass spectrometry as the O-glucuronide of O-desmethyl-4-oxocarbazeran, O-demethylation having taken place at the 6- or 7-position. The corresponding aglycone was identified as the major faecal metabolite. 3. A minor metabolite in urine was identified as the 4-oxo-4'-hydroxy derivative of carbazeran. 4. In animals pretreated with hydralazine, an aldehyde oxidase inhibitor, less radioactivity was extracted in the urine and a significant decrease was observed in the levels of the major urinary metabolite. 5. These results show that aldehyde oxidase plays a key role in the metabolism of carbazeran in guinea pig as it does in man. The similarity of man and guinea pig liver aldehyde oxidase has been observed previously in vitro.

MeSH terms

  • Aldehyde Oxidase
  • Aldehyde Oxidoreductases / metabolism
  • Animals
  • Biotransformation
  • Carbamates / metabolism
  • Carbamates / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Feces / chemistry
  • Guinea Pigs
  • Hydralazine / pharmacology*
  • Hydrolysis
  • Liver / drug effects
  • Liver / enzymology
  • Male

Substances

  • Carbamates
  • carbazeran
  • Hydralazine
  • Aldehyde Oxidoreductases
  • Aldehyde Oxidase