Pharmacokinetics of N1-Acetyl- and N4-Acetylsulphamethoxazole in Man

Abstract

The pharmacokinetics of N1-acetylsulphamethoxazole and N4-acetylsulphamethoxazole in man are described. N1-Acetylsulphamethoxazole is deacetylated to sulphamethoxazole and acetylated to N4-acetylsulphamethoxazole. N4-Acetylsulphamethoxazole is excreted almost unchanged in the urine. The renal excretion rate is independent of the urine flow and urinary pH. N4-Acetylsulphonamides are less lipid soluble and more acidic than their corresponding parent sulphonamides.

Placental transfer and renal clearance of sulphamethoxazole and its metabolite N4‐acetylsulphamethoxazole in a pregnant ewe

“…Protein binding was measured by means of Ultrafree@ Drug Filters (Worthington) in four different plasma samples of the ewe and foetus. High performance liquid chromatography (HPLC) was used to measure the concentration of sulphamethoxazole and its metabolite in the samples of blood and urine (Vree et al, 1978(Vree et al, , 1979(Vree et al, , 1980. The renal excretion rate was obtained by multiplying the urine concentration with the average urine flow over a certain urine collection period.…”

“…As the kidney matures, glomerular filtration increases somewhat faster than tubular secretion and reabsorption. In man, about 10% of the elimination of sulphamethoxazole proceeds by renal excretion via glomerular filtration (minus passive reabsorption), whilst the elimination of the metabolite N4 -acetylsulphamethoxazole proceeds predominantly by renal excretion by means of active tubular secretion (Hekster & Vree, 1982, Vree et al, 1979Jsrgensen & Rasmussen, 1972;Jsrgensen et al, 1974).…”

Renal Tubular Excretion of the N4-Acetyl Metabolites of Sulphasomidine and Sulphadimethoxine in the Dog

“…Plasma and urine samples were analysed for components of interest by HPLC (Vree et al 1979). The following equipment was used: a Spectra-Physics SP 8810 pump with a stainless steel column packed with Spherisorb 5 ODS (25 cm long, 4.6 mm i.d.)…”

“…N4-Acetylsulphasomidine and N4-acetylsulphadimethoxine were synthesized as described by Vree et al (1979). N4-Acetylsulphasomidine contained 5% sulphasomidine (w/w) as determined by high-performance liquid chromatography (HPLC).…”

“…In man, all N4-acetylsulphonamides that have been studied so far, are excreted by an active tubular transport mechanism (Vree & Hekster 1987). Co-administration of probenecid lowers this excretion, indicating transport via the organic anion transport mechanism (Vree et al 1979).…”