THE PHARMACOLOGY OF THE ANTIMALARIAL DRUG 4,4'-DIFORMAMIDODIPHENYLSULFONE (DFD) IN MAN

¹ Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, Florida

4,4'-Diformamidodiphenylsulfone (DFD) was given to six human volunteers as a single 1600-mg p.o. dose. Maximum plasma levels were 2.9 ± 0.6 µg/ml at five to eight hours with a T, of 24 to 36 hours. No difference was seen among plasma levels of total amine, free amine or ³⁵S-sulfone, indicating all plasma drug consists of 4, 4'-diaminodiphenylsulfone. DFD is deformylated at a rapid rate. Loss of ¹⁴CO₂ in expired air was 50% complete six to eight hours after ¹⁴C-formyl-DFD administration. Analysis of plasma after ¹⁴C-formyl-DFD administration demonstrated less than 10% of plasma drug to be formyl derivatives. Urinary excretion of total amine was 12.7 ± 2.3% of dose with 31 to 71% of urinary metabolites as free amine. The amount of drug deformylated agreed well with urinary excretion of total amine. Biliary excretion accounted for 13 to 25% of absorbed drug. DFD thus represents a way of administering 4,4'-diaminodiphenylsulfone, characterized by low oral absorption and low sustained plasma levels. Whether this conveys an advantage in terms of efficacy and lower toxicity can Only be evaluated in the field.