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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 (2. 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
Volume12
Issue number2
StatePublished - 1984
Externally publishedYes

Fingerprint

tiazofurin
Metabolism
Rodentia
Dogs
Rabbits
Pharmaceutical Preparations
Half-Life
Pharmacokinetics
Muscle
Rats
Phosphates
Inhibitory Concentration 50
Plasmas
Skeletal Muscle
Injections

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Arnold, S. T., Jayaram, H. N., Harper, G. R., Litterst, C. L., Malspeis, L., DeSouza, J. J., ... Cooney, D. A. (1984). The disposition and metabolism of tiazofurin in rodents, rabbits, and dogs. Drug Metabolism and Disposition, 12(2), 165-173.

The disposition and metabolism of tiazofurin in rodents, rabbits, and dogs. / Arnold, S. T.; Jayaram, H. N.; Harper, G. R.; Litterst, C. L.; Malspeis, L.; DeSouza, J. J.; Staubus, A. E.; Ahluwalia, G. S.; Wilson, Y. A.; Cooney, D. A.

In: Drug Metabolism and Disposition, Vol. 12, No. 2, 1984, p. 165-173.

Research output: Contribution to journalArticle

Arnold, ST, Jayaram, HN, Harper, GR, Litterst, CL, Malspeis, L, DeSouza, JJ, Staubus, AE, Ahluwalia, GS, Wilson, YA & Cooney, DA 1984, 'The disposition and metabolism of tiazofurin in rodents, rabbits, and dogs', Drug Metabolism and Disposition, vol. 12, no. 2, pp. 165-173.
Arnold ST, Jayaram HN, Harper GR, Litterst CL, Malspeis L, DeSouza JJ et al. The disposition and metabolism of tiazofurin in rodents, rabbits, and dogs. Drug Metabolism and Disposition. 1984;12(2):165-173.
Arnold, S. T. ; Jayaram, H. N. ; Harper, G. R. ; Litterst, C. L. ; Malspeis, L. ; DeSouza, J. J. ; Staubus, A. E. ; Ahluwalia, G. S. ; Wilson, Y. A. ; Cooney, D. A. / The disposition and metabolism of tiazofurin in rodents, rabbits, and dogs. In: Drug Metabolism and Disposition. 1984 ; Vol. 12, No. 2. pp. 165-173.
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