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Pharmaceutisch Weekblad

, Volume 13, Issue 5, pp 198–206 | Cite as

Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfamethomidine in humans

  • T. B. Vree
  • E. W. J. Beneken Kolmer
  • Y. A. Hekster
Articles

Abstract

Sulfamethomidine metabolism was studied in 6 volunteers. In humans, only N1-glucuronidation and N4-acetylation take place, leading to the final double conjugate N4-acetylsulfamethomidine N1-glucuronide. The N1-glucuronides were directly measured by high pressure liquid chromatography. Fast and slow acetylators show a similar half-life for sulfamethomidine (26±6 h) and its conjugates sulfamethomidine N1-glucuronide (26±6 h) and N4-acetylsulfamethomidine (36±16 h). Approximately 50–60% of the oral dose of sulfamethomidine is excreted in the urine, leaving 40–50% for excretion into bile and faeces. The main metabolite of sulfamethomidine is its N1-glucuronide, which accounts for 36±7% of the dose, followed by N4-acetylsulfamethomidine (16±8%). N1-glucuronidation results in a 75% decrease in protein binding of sulfamethomidine. N4-acetylsulfamethomidine and its N1-glucuronide showed the same high protein binding of 99%. The renal clearance of N4-acetylsulfamethomidine is 7.9±2.2 ml/min and approximately 20 times as high as that of the parent drug (0.46±0.16 ml/min). Total body clearance of sulfamethomidine is 4.5±0.9 ml/min and the volume of distribution in steady state 10.6±1.7 1. No measurable plasma concentrations of the N1-glucuronides from sulfamethomidine are found in plasma. This may be explained by renal glucuronidation after active tubular reabsorption.

Keywords

Clearance, renal Clinical trials Glucuronidation Metabolism Pharmacokinetics Protein binding Sulfamethomidine 
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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1991

Authors and Affiliations

  • T. B. Vree
    • 1
  • E. W. J. Beneken Kolmer
    • 1
  • Y. A. Hekster
    • 1
  1. 1.Department of Clinical PharmacyUniversity Hospital Nijmegen Sint RadboudHB Nijmegenthe Netherlands

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