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Pharmaceutisch Weekblad

, Volume 5, Issue 2, pp 49–56 | Cite as

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
  • T. B. Vree
  • Y. A. Hekster
  • M. W. Tijhuis
  • M. Baakman
  • T. J. Janssen
  • E. F. S. Termond
Original Articles

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.

Keywords

Public Health Sulfonamide Methyl Internal Medicine Molecular Structure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1983

Authors and Affiliations

  • T. B. Vree
    • 1
  • Y. A. Hekster
    • 1
  • M. W. Tijhuis
    • 1
  • M. Baakman
    • 1
  • T. J. Janssen
    • 1
  • E. F. S. Termond
    • 1
  1. 1.Department of Clinical Pharmacy, Sint Radboud HospitalUniversity of NijmegenGA NijmegenThe Netherlands

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