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

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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.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Department of Anaesthesiology, University Hospital Nijmegen, P.O. Box 9101, 6500, HB Nijmegen, The Netherlands

    T. B. Vree

  2. Department of Clinical Pharmacy, University Hospital Nijmegen, P.O. Box 9101, 6500, HB Nijmegen, The Netherlands

    E. W. J. Beneken Kolmer, M. Martea, R. Bosch &  Y. A. Hekster

  3. Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Fuchu, 183, Tokyo, Japan

    M. Shimoda

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  1. T. B. Vree
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  2. E. W. J. Beneken Kolmer
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  3. M. Martea
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  4. R. Bosch
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  5. Y. A. Hekster
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  6. M. Shimoda
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Vree, T.B., Beneken Kolmer, E.W.J., Martea, M. et al. Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man. Pharmaceutisch Weekblad Scientific Edition 12, 51–59 (1990). https://doi.org/10.1007/BF01970146

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