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Gastrointestinal metabolism of N‐acetylcysteine in the rat, including an assay for sulfite in biological systems
Author(s) -
Cotgreave Ian A.,
Berggren Margareta,
Jones Thomas W.,
Dawson Janet,
Moldéus Peter
Publication year - 1987
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510080408
Subject(s) - acetylcysteine , glutathione , cysteine , chemistry , bioavailability , pharmacology , metabolism , pharmacokinetics , metabolite , cysteine metabolism , drug metabolism , in vivo , sulfite , biochemistry , toxicity , antioxidant , medicine , biology , enzyme , microbiology and biotechnology , organic chemistry
The intestinal metabolism of N‐acetylcysteine was studied in the rat. Isolated intestinal epithelial cells were shown to rapdily deacetylate [ 14 C]‐N‐acetylcysteine to [ 14 C]‐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 [ 14 C]‐N‐acetylcysteine (50mg/kg; 25μCi) in vivo into the ilium, small quantities of both reduced and oxidized [ 14 C]‐N‐acetylcysteine were demonstrated in hepatic portal vein plasma. [ 14 C]‐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, [ 14 C]‐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.