Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2'-deoxycoformycin in beagle dogs

Larry E. Rodman, Daniel R. Farnell, John M. Coyne, Paula W. Allan, Donald L. Hill, Kimberly L.K. Duncan, Joseph E. Tomaszewski, Adaline C. Smith, John G. Page

Research output: Contribution to journalArticle

Abstract

For 3 consecutive days, the nucleoside cordycepin (3'-deoxyadenosine) was administered as 1-hr iv infusions (0, 1, 4, 8, 10, or 20 mg/kg/day) to dogs. These doses were given 1 hr after a bolus iv injection 0.25 mg/kg/day) of 2'-deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase. The hypothesis was that dCF would affect the toxicity of cordycepin. Plasma adenosine deaminase activity was strongly inhibited during the dose period and for 5 days following the final dose of dCF. Dogs given cordycepin alone showed no drug-related toxicities. In dogs given only dCF, drug-related toxicity to lymphoid tissue (lymphopenia and thymus lymphoid depletion), thrombocytopenia, and decreases in food consumption were observed. Cordycepin in combination with dCF produced symptoms associated with severe gastrointestinal toxicity (decreased body weights, emesis, diarrhea, decreased food consumption, and necrosis of the gastrointestinal tract) and bone marrow toxicity (lymphopenia, thrombocytopenia, and depletion of hematopoietic cells). The gastrointestinal tract and bone marrow were sites associated with dose-limiting toxicities. In surviving dogs, most of the effects were reversible by Day 30. The maximum tolerated dose of cordycepin administered in combination with dCF was 8 mg/kg/day (160 mg/m2/day) given daily for 3 days.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalToxicology and Applied Pharmacology
Volume147
Issue number1
DOIs
StatePublished - Nov 1997

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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    Rodman, L. E., Farnell, D. R., Coyne, J. M., Allan, P. W., Hill, D. L., Duncan, K. L. K., Tomaszewski, J. E., Smith, A. C., & Page, J. G. (1997). Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2'-deoxycoformycin in beagle dogs. Toxicology and Applied Pharmacology, 147(1), 39-45. https://doi.org/10.1006/taap.1997.8264