Alterations in erythrocyte adenine nucleotide pools resulting from 2'-deoxycoformycin therapy.
2'-Deoxycoformycin, a tight-binding adenosine deaminase inhibitor, was administered to 11 adult patients with refractory lymphoproliferative diseases. Total doses ranged from 1.0 to 13.5 mg/kg. Inhibition of lymphoblast adenosine deaminase was obtained in all cases and tumor cytoreduction was noted in eight of ten cases, but no clinically meaningful remissions were obtained. Major toxicities occurred in five patients and included pulmonary edema, renal failure, central nervous system toxicity, hypotension, and death. Toxicity prevented retreatment in several cases in which marked cytoreduction occurred. Deoxyadenosine triphosphate accumulated to a variable extent in the red blood cells of all patients, and a reciprocal decrease in erythrocyte adenosine triphosphate was noted in all cases but one. All patients who suffered major organ toxicity had red blood cell deoxyadenosine triphosphate/adenosine triphosphate ratios greater than 1.3. These data suggest that the degree of replacement of adenosine triphosphate by deoxyadenosine triphosphate in erythrocytes reflects the biochemical milieu which may result in systemic toxicity following treatment with 2'-deoxycoformycin.
D000227:Adenine Nucleotides / Q000097:blood*; D058892:Adenosine Deaminase Inhibitors; D000293:Adolescent; D000328:Adult; D000368:Aged; D003070:Coformycin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015649:Pentostatin; D012263:Ribonucleosides / Q000627:therapeutic use*
D000227:Adenine Nucleotides; D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin