Effects of methoxy groups in the NI-substituent of sulfonamides on the pathways of elimination in man. The acetylation-deacetylation equilibrium and mechanisms of renal excretion of sulfisomidine, sulfamethomidine and sulfadimethoxine.
Sulfisomidine, sulfamethomidine, sulfadimethoxine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation and those of protein binding, the half-lives of elimination and the apparent and true renal clearance values were measured. No acetylation phenotype could be demonstrated in these compounds. Methoxy substitution in the NI-pyrimidine group of sulfisomidine affects predominantly the renal clearance value and mechanism of the parent compound but has no influence on the renal clearance of the N4-acetyl derivatives. The renal clearance value of sulfisomidine is 232 +/- 33 ml/min, of sulfamethomidine 21.60 +/- 16.4 ml/min and of sulfadimethoxine 10.87 +/- 10.44 ml/min. The renal clearance values of the corresponding N4-acetylsulfonamide derivatives are 314 +/- 91 ml/min, 342 +/- 63 ml/min and 202 +/- 65 ml/min respectively. Tubular reabsorption, caused by methoxy substitution in the NI-pyrimidine ring, lowers the rate of elimination and increases the half-life. The half-life of sulfisomidine is 8.5 +/- 0.5 h, of sulfamethomidine 27.8 +/- 5.3 h and of sufadimethoxine 34.6 +/- 10.4 h.
D000107:Acetylation; D000328:Adult; D003640:Dealkylation; D005260:Female; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010641:Phenotype; D013329:Structure-Activity Relationship; D013412:Sulfadimethoxine / Q000652:urine; D013424:Sulfanilamides / Q000652:urine; D013443:Sulfisomidine / Q000652:urine; D013449:Sulfonamides / Q000378:metabolism* / Q000652:urine
D013424:Sulfanilamides; D013449:Sulfonamides; D013412:Sulfadimethoxine; C043086:sulfamethomidine; D013443:Sulfisomidine