Metabolism of 1,3-di-{4-[N-(4,6-dimethyl-2-pyrimidinyl)sulphamoyl]phenyl}triazene (DDPSPT) in the rat

Abstract

1. Six hours after rats were orally dosed with 1,3-di-{4-[N-(4,6-dimethyl-2-pyrimidinyl)sulphamoyl][U-¹⁴C]phenyl},triazene (¹⁴ approx. 81% of the ¹⁴C remained in the gastrointestinal tract (gut) and less than 3% was excreted in the urine.

2. Six hours after dosing, more than half of the ¹⁴C in the gut was present as DDPSPT. ¹⁴C-Labelled metabolites in the gut included 4-amino-N-{4,6-dimethyl-2-pyrimidinyl)-benzenesulphonamide (Sulmet), N⁴-glucosyl-N-(4,6-dimethyl-2-pyrimidinyl)ben-zenesulphonamide (N⁴-gluc-Sulmet), 4-acetamido- N-(4,6-dimethyl-2-pyrimidinyl)ben-zenesulphonamide (N⁴acetyl-Sulmet), and [N-4,6-dimethyl-2-pyrimidinyl)ben-zenesulphonamide] (desamino-Sulmet).

3. ¹⁴C-Labelled compounds in the blood, liver and skeletal muscle included DDPSPT. Sulmet, N⁴-gluc-Sulmet, N⁴-acetyl-Sulmet and desamino-Sulmet.

4. There was little or no reaction of DDPSPT with cysteine, bovine serum albumin. AMP, GMP, or calf thymus deoxyribonucleic acid in vitro (pH 3, 5, 7 or 8).