The clinical pharmacology of the adenosine deaminase inhibitor 2'-deoxycoformycin.
2'-deoxycoformycin (2'-dCF; Pentostatin), a stoichiometric inhibitor of mammalian adenosine deaminase (ado deaminase), exhibits immunosuppressive and antilymphocytic activity in animal test systems. A clinical pharmacology/phase I study of 2'-dCF administered as a single agent has been completed (18 patients). Dose levels ranged from 0.1 mg/kg X 1 to 0.25 mg/kg/day X 5; ado deaminase and 2'-dCF were measured spectrophotometrically. Plasma decay curves were bi-exponential (alpha and beta t 1/2 values about 1 and 10 h respectively). Recovery of unchanged 2'-dCF from urine (48 h) was 32%--48% of the administered drug. Major toxic manifestations were lymphocytopenia (all patients) and urate nephropathy (1 patient, with subsequent patients in the series receiving allopurinol, 300 mg/day). Three partial responses were seen in seven patients with acute lymphocytic leukaemia receiving 0.25 mg 2'-dCF/kg/day X 5.
D058892:Adenosine Deaminase Inhibitors; D000328:Adult; D000368:Aged; D000818:Animals; D003070:Coformycin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D012263:Ribonucleosides / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood
D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D003070:Coformycin; D014527:Uric Acid; D015649:Pentostatin; D009700:Nucleoside Deaminases