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

Pharmaceutisch Weekblad. Scientific Edition
T B VreeM Shimoda

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.

References

Dec 1, 1977·The Australian Journal of Experimental Biology and Medical Science·J D Baggot
Jan 1, 1989·Clinical Pharmacokinetics·C A van Ginneken, F G Russel
Apr 1, 1989·Nihon juigaku zasshi. The Japanese journal of veterinary science·T B VreeK Hoji
Jul 1, 1988·European Journal of Drug Metabolism and Pharmacokinetics·B Ahmad, J W Powell
Mar 1, 1988·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M G BarronM O James
Aug 1, 1986·Journal of Pharmaceutical Sciences·P Veng-Pedersen
Oct 1, 1986·Nihon juigaku zasshi. The Japanese journal of veterinary science·Y Takahashi
Feb 1, 1986·Nihon juigaku zasshi. The Japanese journal of veterinary science·Y Takahashi
Jan 1, 1972·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S R Walker, R T Williams
Oct 1, 1968·The Biochemical Journal·J W BridgesR T Williams
Jun 1, 1970·The Biochemical Journal·R H AdamsonR T Williams
May 1, 1972·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P C HiromR T Williams
Dec 1, 1970·Nihon juigaku zasshi. The Japanese journal of veterinary science·T OnoderaY Oshima
Sep 1, 1965·The Biochemical Journal·J W BridgesR T Williams
Apr 1, 1964·Nihon juigaku zasshi. The Japanese journal of veterinary science·Y OshimaM Mogi
Sep 1, 1984·Journal of Pharmaceutical Sciences·J W HubbardD Smith
Jun 1, 1983·Journal of Veterinary Pharmacology and Therapeutics·T B VreeJ F Nouws

Citations

Oct 18, 1991·Pharmaceutisch Weekblad. Scientific Edition·T B VreeY A Hekster
Nov 7, 2001·Journal of Veterinary Pharmacology and Therapeutics·W F KhalilE Kokue
Feb 1, 1994·Journal of Veterinary Pharmacology and Therapeutics·T B VreeJ F Nouws
Oct 16, 1992·Pharmaceutisch Weekblad. Scientific Edition·T B VreeY A Hekster
Dec 31, 1997·The Veterinary Quarterly·M ShimodaD S Son
Oct 1, 1991·The Veterinary Quarterly·T B VreeA Peeters
Nov 1, 1992·The Annals of Pharmacotherapy·T B VreeP G Anderson
Jan 1, 1992·Biopharmaceutics & Drug Disposition·T B VreeT Miura

Related Concepts

Acetylation
High Pressure Liquid Chromatography Procedure
Dealkylation
Glucuronic Acids
Half-Life
Plasma Protein Binding Capacity
Deposul

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