Clinical pharmacology of deoxycoformycin.
Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA). Twenty-one courses of DCF were administered to 13 patients ranging in age from 15 to 78 yr. Eight patients had T-cell disorders, and five patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5 to 30 mg/sq m/day, and the duration of the courses ranged from 1 to 5 days. The DCF plasma half-life ranged from 4.9 to 6.2 hr and was independent of dose. The dose-limiting toxicities involved the central nervous system (CNS) and the kidneys. Other toxicities included bronchitis, decreases in hematocrit, arthralgias, and myalgias. Mortality was encountered in three patients. These toxic effects may have been secondary to the accumulation of the metabolites adenosine and deoxyadenosine. Deoxyadenosine and adenosine were both detectable in plasma (10(-6) M) and in urine (10(-3) M). Two partial remissions were observed: one in a patient with T-cell ALL and another in a patient with mycosis fungoides. Minimal responses characterized by either declines in peripheral blast counts or partial resolution of adenopathy were observed in five other patients. No responses were observed in six patients. These observations suggest that DCF is effective in the treatment of T-cell lymphoid malignancies.
D000241:Adenosine / Q000097:blood; D058892:Adenosine Deaminase Inhibitors; D000248:Adenosine Kinase / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D001991:Bronchitis / Q000139:chemically induced; D003070:Coformycin / Q000031:analogs & derivatives / Q000627:therapeutic use* / Q000633:toxicity; D003128:Coma / Q000139:chemically induced; D003231:Conjunctivitis / Q000139:chemically induced; D003839:Deoxyadenosines / Q000097:blood; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D010770:Phosphotransferases / Q000097:blood; D017853:Phosphotransferases (Alcohol Group Acceptor); D012263:Ribonucleosides / Q000627:therapeutic use*
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000248:Adenosine Kinase; C020005:deoxyadenosine kinase; D009700:Nucleoside Deaminases; D000241:Adenosine