Abstract
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 N1-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 N1-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 sulfadimethoxine 34.6±10.4 h.
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Vree, T.B., Hekster, Y.A., Tijhuis, M.W. et al. Effects of methoxy groups in the N1-substituent of sulfonamides on the pathways of elimination in man. Pharmaceutisch Weekblad Scientific Edition 6, 150–156 (1984). https://doi.org/10.1007/BF01954042
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DOI: https://doi.org/10.1007/BF01954042