Effects of a new adenosine deaminase inhibitor, isocoformycin, on toxicity, antitumor activity and tissue distribution of formycin A and 9-beta-D-arabinofuranosyladenine.
Single intraperitoneal and intravenous injections of isocoformycin at 1,200 mg/kg did not cause the death of mice. Isocoformycin which inhibited adenosine deaminase enhanced significantly the toxicity of formycin A and ara-A at various combination ratios. Isocoformycin potentiated antitumor activity of formycin A and ara-A against L1210 leukemia. Formycin A and ara-A disappeared rapidly from the blood and tissues and could not be found in any tissues even 0.5 hour after a single intraperitoneal injection. However, when used in combination with isocoformycin both were detected in the blood and tissues, especially at high concentration in liver and kidney. These indicate that the deamination of formycin A and ara-A is blocked by isocoformycin in vivo.
D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000970:Antineoplastic Agents; D003070:Coformycin / Q000494:pharmacology* / Q000633:toxicity; D004357:Drug Synergism; D005260:Female; D005573:Formycins / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D012263:Ribonucleosides / Q000494:pharmacology*; D014018:Tissue Distribution; D014740:Vidarabine / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*
D058892:Adenosine Deaminase Inhibitors; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D005573:Formycins; D012263:Ribonucleosides; D003070:Coformycin; C025528:isocoformycin; D009700:Nucleoside Deaminases; D014740:Vidarabine