The disposition and metabolism of tiazofurin in rodents, rabbits, and dogs

S. T. Arnold, H. N. Jayaram, G. R. Harper, C. L. Litterst, L. Malspeis, J. J. DeSouza, A. E. Staubus, G. S. Ahluwalia, Y. A. Wilson, D. A. Cooney

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25 Scopus citations


The pharmacokinetics and metabolism of tiazofurin (2-β-D-ribofuranosylthiazole-4-carboxamide) have been examined in the mouse, rat, rabbit, and dog using tritiated drug as a marker. In all four species, tiazofurin, given as a single bolus iv injection, is removed from the circulation in a triphasic manner, with a generally prolonged terminal half-life. In all cases, the mean concentration of unchanged drug prevailing during this terminal phase was well within the cytotoxic range (IC50 vs. P388 cells is 2 μM in vitro). Urinary excretion accounted for between ~40 and 90% of the administered dose in all four species, with only minor quantities (<3%) of drug-derived radioactivity detected in the feces. The metabolism of tiazofurin was examined in mice and rats: although no evidence was uncovered for hydroxylation of tiazofurin at carbon atom 5 of the thiazole ring, phosphorylation of the drug at its 5'-hydroxyl was demonstrable in nearly every organ of both species, but, liver, striated muscles, and kidney were the only tissues catalyzing the synthesis of thiazole-4-carboxamide adenine dinucleotide to any prominent degree. This synthesis did not appear to be a saturated process, even at doses as high as 8000 mg/m2. Since rodent skeletal muscle accumulated high concentrations of tiazofurin phosphates in vivo, it is suggested that musculature may serve as a reservoir for the drug, and contribute to its rather protracted terminal half-life in plasma.

Original languageEnglish (US)
Pages (from-to)165-173
Number of pages9
JournalDrug Metabolism and Disposition
Issue number2
StatePublished - Jun 22 1984

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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