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Pharmaceutisch Weekblad

, Volume 12, Issue 2, pp 51–59 | Cite as

Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man

  • T. B. Vree
  • E. W. J. Beneken Kolmer
  • M. Martea
  • R. Bosch
  • Y. A. Hekster
  • M. Shimoda
Original Articles

Abstract

Sulfadimethoxine is metabolized byO-dealkylation, N4-acetylation and N1-glucuronidation. In man, only N1-glucuronidation and N4-acetylation takes place, leading to the final double conjugate N4-acetylsulfadimethoxine-N1-glucuronide. The N1-glucuronides are directly measured by high pressure liquid chromatography. When N4-acetylsulfadimethoxine is administered as parent drug, 30% of the dose is N1-glucuronidated and excreted. Fast acetylators show a shorter half-life for sulfadimethoxine than slow acetylators (27.8±4.2 h versus 36.3±5.4 h; P=0.013), similarly the half-life of the N4-acetyl conjugate is also shorter in fast acetylators (41.3±5.2 h versus 53.5±8.5 h, P=0.036). No measurable plasma concentrations of the N1-glucuronides from sulfadimethoxine are found in plasma. N1-glucuronidation results in a 75% decrease in protein binding of sulfadimethoxine. N4-acetylsulfadimethoxine and its N1-glucuronide showed the same high protein binding of 99%. Approximately 50–60% of the oral dose of sulfadimethoxine is excreted in the urine, leaving 40–50% for excretion into bile and faeces.

Keywords

Chromatography, high pressure liquid Clearance Metabolism Pharmacokinetics Protein binding Sulfadimethoxine 

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1990

Authors and Affiliations

  • T. B. Vree
    • 1
  • E. W. J. Beneken Kolmer
    • 2
  • M. Martea
    • 2
  • R. Bosch
    • 2
  • Y. A. Hekster
    • 2
  • M. Shimoda
    • 3
  1. 1.Department of Clinical Pharmacy and Department of AnaesthesiologyUniversity Hospital NijmegenHB NijmegenThe Netherlands
  2. 2.Department of Clinical PharmacyUniversity Hospital NijmegenHB NijmegenThe Netherlands
  3. 3.Department of Veterinary MedicineTokyo University of Agriculture and TechnologyTokyoJapan

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