Effects of a new adenosine deaminase inhibitor, isocoformycin, on toxicity, antitumor activity and tissue distribution of formycin A and 9-.BETA.-D-arabinofuranosyladenine.

Abstract
Single i.p. and i.v. injections of 1200 mg/kg isocoformycin did not cause the death of mice. Isocoformycin inhibited adenosine deaminase and significantly enhanced the toxicity of formycin A and ara-A [9-.beta.-D-arabinofuranosyladenine] at various combination ratios. Isocoformycin potentiated the antitumor activity of formycin A and ara-A against [mouse] L-1210 leukemia cells. Formycin A and ara-A disappeared rapidly from the blood and tissues and could not be found in any tissues 0.5 h after a single i.p. injection. When used in combination with isocoformycin, both were detected in the blood and tissues, especially at high concentration in liver and kidney. The deamination of formycin A and ara-A is probably blocked by isocoformycin in vivo.