Formation and elimination of sulphamethoxazole hydroxylamine after oral administration of sulphamethoxazole

• Published in: British journal of clinical pharmacology Vol. 38; no. 2; pp. 147 - 150
• Main Authors: Ven, AJ, Mantel, MA, Vree, TB, Koopmans, PP, Meer, JW
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.1994; Blackwell Science
• Subjects: Acetylation; Administration, Oral; Adult; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Chromatography, High Pressure Liquid; European Continental Ancestry Group; Female; Half-Life; Humans; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Pharmacology. Drug treatments; Phenotype; Sulfamethoxazole - administration & dosage; Sulfamethoxazole - analogs & derivatives; Sulfamethoxazole - blood; Sulfamethoxazole - pharmacokinetics; Sulfamethoxazole - urine; Human; Sulfanilamide derivatives; Single dose; Oral administration; Antibacterial agent; Metabolism; Normal; Pharmacokinetics
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/j.1365-2125.1994.tb04339.x

The formation and elimination of sulphamethoxazole hydroxylamine in relation to the pharmacokinetics of the parent compound and its N4‐ acetyl metabolite were investigated in six healthy subjects after a single oral dose of 800 mg sulphamethoxazole. The apparent half‐lives of sulphamethoxazole and its metabolites were approximately 10 h, indicative of formation rate‐limited metabolism. The mean residence time of the hydroxylamine metabolite was 5.5 +/‐ 1.5 h. The renal clearance of sulphamethoxazole hydroxylamine was 4.39 +/‐ 0.91 l h‐1. The urinary recovery of sulphamethoxazole accounted for 16.5 +/‐ 5.5% of the dose, N4‐acetyl‐sulphamethoxazole for 46.2 +/‐ 6.6% and the hydroxylamine metabolite for 2.4 +/‐ 0.8%. The remaining 35% of the dose was unaccounted for. Acetylator phenotype was determined using sulphadimidine. The renal excretion of sulphamethoxazole hydroxylamine was 1.9 +/‐ 0.9% in slow acetylators (n = 3) and 2.8 +/‐ 0.3% in fast acetylators (n = 3); for N4‐acetyl‐sulphamethoxazole the values were 48 +/‐ 6% and 44 +/‐ 8%, respectively. Sulphamethoxazole is metabolized, although to a limited extent, to a hydroxylamine metabolite. This metabolite may be important for the pathogenesis of adverse reactions.