The clinical pharmacology of the adenosine deaminase inhibitor 2?-deoxycoformycin

Abstract

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/kgx1 to 0.25 mg/kg/dayx5; ado deaminase and 2′-dCF were measured spectrophotometrically. Plasma decay curves were bi-exponential (α and βt_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/dayx5.