The effect of the molecular structure of closely related N1-substituents of sulfonamides on the pathways of elimination in man. The acetylation-deacetylation equilibrium and renal clearance related to the structure of sulfadiazine, sulfamerazine and sulfadimidine.
Sulfadiazine, sulfamerazine, sulfadimidine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation, protein binding, half-lives of elimination and apparent and true renal clearance values were measured. Methyl substitution in the N1-pyrimidine ring favours acetylation by an additional N-acetyltransferase isoenzyme present in 'fast' acetylators only. Methyl substitution in the N1-pyrimidine ring favours renal clearance of the N4-acetylsulfonamide derivatives. The N1-substituent probably reinforces the binding of the N4-acetyl group to the active tubular transport mechanism. The renal clearance of these sulfonamides is not dependent on the structure of the N1-substituent.
D000107:Acetylation; D000328:Adult; D003640:Dealkylation; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010641:Phenotype; D011485:Protein Binding; D013411:Sulfadiazine / Q000378:metabolism; D013416:Sulfamerazine / Q000378:metabolism; D013418:Sulfamethazine / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism*
D013449:Sulfonamides; D013411:Sulfadiazine; D013418:Sulfamethazine; D013416:Sulfamerazine