Abstract

4,4'-Diformamidodiphenylsulfone (DFD), 30 to 60 mg/kg, was studied in dog and monkey in an attempt to define its chemotherapeutic role in relation to the parent 4,4'-diaminodiphenylsulfone (DDS). Differences in crystal morphology and solubility were found for various DFD preparations which can give rise to differences in handling of radioactive tracer and nonradioactive drug. DFD plasma binding was similar to DDS. DFD given i.v. in dimethylsulfoxide to dogs was rapidly deformylated with concurrent increase in DDS in plasma. After nine hours formyl derivatives were less than 10% of plasma total amine. Urinary excretion after i.v. DFD to dog showed 18% of dose as formyl derivatives equally divided between mono- and diformyl compounds. Approximately half the DFD dose was excreted as DDS and its conjugates. DFD had maximum oral absorption in dogs of 5% compared with 69% for DDS and in monkey 18% compared with 51% for DDS. Plasma concentrations of total sulfone after oral DFD were one tenth those obtained for similar doses of DDS. Methemoglobin production by DFD, DDS and the hydroxylamine derivatives of DDS were compared. N-hydroxylation of DFD and DDS appeared to be a minor metabolic pathway. It was concluded that the main pharmacological and chemotherapeutic effects of DFD are attributable to DDS formed in vivo.