Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion

Gerald Batist, Raymond W. Klecker, Hiremagalur N. Jayaram, Jean F. Jenkins, John Grygiel, Daniel C. Ihde, Joyce L. Eddy, Robert L. Fine, Ian G. Kerr, Jerry M. Collins

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Tiazofurin (2-β-D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M2. Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.

Original languageEnglish (US)
Pages (from-to)349-355
Number of pages7
JournalInvestigational New Drugs
Volume3
Issue number4
DOIs
StatePublished - Dec 1985
Externally publishedYes

Fingerprint

tiazofurin
Pharmacokinetics
Lethargy
Allopurinol
Myalgia
Uric Acid
Tumor Cell Line
Chest Pain
Nucleosides
Human Activities
Pharmaceutical Preparations
Half-Life
High Pressure Liquid Chromatography
Kidney
Skin
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Batist, G., Klecker, R. W., Jayaram, H. N., Jenkins, J. F., Grygiel, J., Ihde, D. C., ... Collins, J. M. (1985). Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion. Investigational New Drugs, 3(4), 349-355. https://doi.org/10.1007/BF00170757

Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion. / Batist, Gerald; Klecker, Raymond W.; Jayaram, Hiremagalur N.; Jenkins, Jean F.; Grygiel, John; Ihde, Daniel C.; Eddy, Joyce L.; Fine, Robert L.; Kerr, Ian G.; Collins, Jerry M.

In: Investigational New Drugs, Vol. 3, No. 4, 12.1985, p. 349-355.

Research output: Contribution to journalArticle

Batist, G, Klecker, RW, Jayaram, HN, Jenkins, JF, Grygiel, J, Ihde, DC, Eddy, JL, Fine, RL, Kerr, IG & Collins, JM 1985, 'Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion', Investigational New Drugs, vol. 3, no. 4, pp. 349-355. https://doi.org/10.1007/BF00170757
Batist, Gerald ; Klecker, Raymond W. ; Jayaram, Hiremagalur N. ; Jenkins, Jean F. ; Grygiel, John ; Ihde, Daniel C. ; Eddy, Joyce L. ; Fine, Robert L. ; Kerr, Ian G. ; Collins, Jerry M. / Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion. In: Investigational New Drugs. 1985 ; Vol. 3, No. 4. pp. 349-355.
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