Gastrointestinal metabolism of N-acetylcysteine in the rat, including an assay for sulfite in biological systems
✍ Scribed by Ian A. Cotgreave; Margareta Berggren; Thomas W. Jones; Janet Dawson; Peter Moldéus
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 422 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
The intestinal metabolism of N-acetylcysteine was studied in the rat. Isolated intestinal e ithelial cells were shown to rapdily deacetylate [ ''C]-N-acetylcysteine to [&I-cysteine, with slight oxidation of the latter to disulfide species. The cells did not accumulate reduced or oxidized cysteine, and N-acetylcysteine itself was not detected either free or in oxidized species intracellularly. Further metabolism of this NAC-derived cysteine to inorganic sulfite or glutathione was not detected. Following the administration of ['4C]-N-acetylcysteine (50m ikg; 25pCi) in vivo into the ilium, small quantities of both reduced and oxidized [ I C]-N-acetylcysteine were demonstrated in hepatic portal vein plasma. ['4C]-cysteine and inorganic sulfite were demonstrated as the major metabolites of N-acetylcysteine. These were present in the portal vein plasma at levels five and three times greater than the parent drug, respectively, 30 min after dosing. Additionally, ["CC]-glutathione was shown to be a minor metabolite of N-acetylcysteine accumulating in portal vein plasma.
These results may provide an explanation for the apparent low bioavailability of N-acetylcysteine when administered orally in humans and are discussed in terms of the origins of the protective effect of the drug in cases of paracetamol intoxication in humans.