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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

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Abstract

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.

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Vree, T.B., Hekster, Y.A., Tijhuis, M.W. et al. The effect of the molecular structure of closely related N1-substituents of sulfonamides on the pathways of elimination in man. Pharmaceutisch Weekblad Scientific Edition 5, 49–56 (1983). https://doi.org/10.1007/BF01960075

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  • DOI: https://doi.org/10.1007/BF01960075

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