title: Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man.
abstract: Sulfadimethoxine is metabolized by O-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.
authors.affiliation: Department of Clinical Pharmacy, University Hospital Nijmegen, The Netherlands.
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: E W
authors.initials: EW
authors.lastname: Beneken Kolmer
authors.forename: M
authors.initials: M
authors.lastname: Martea
authors.forename: R
authors.initials: R
authors.lastname: Bosch
authors.forename: Y A
authors.initials: YA
authors.lastname: Hekster
authors.forename: M
authors.initials: M
authors.lastname: Shimoda
mesh_terms: D000107:Acetylation; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011485:Protein Binding; D013412:Sulfadimethoxine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine
chemical_list: D005965:Glucuronates; D013412:Sulfadimethoxine