Pharmacokinetics and mechanism of renal excretion of short acting sulphonamides and N4-acetylsulphonamide derivatives in man

Abstract

The pharmacokinetics of short acting sulphonamides and a series of N4-acetylsulphonamide derivatives has been investigated. Sulphonamides with a sulphur atom two atomic bond distances from the N1 atom are excreted by active tubular secretion, e.g. sulphamethizole, sulphaethidole and sulphathiasole. When the sulphur atom is replaced by an oxygen or nitrogen atom, active renal excretion no longer occurs. N4-acetylsulphonamides are excreted by active tubular secretion. The renal clearance values of the N4-acetylsulphonamides are not influenced by the substituent at the N1 position. Two groups of N4-acetylsulphonamides can be distinguished. One has a T1/2 of 4-6 h and a renal clearance value of 20-60 ml/min and the second has a T1/2 of 10-20 h and a renal clearance of less than 10 ml/min. N4-acetylsulphonamides are deacetylated to the extent of about 5%.

Effect of age on the acetylation and deacetylation reactions of sulphadimidine and N4‐ acetylsulphadimidine in calves

“…In man, the elimination of SDM is largely the result of acetylation, and the metabolite Nq-SDM is predominantly excreted by active tubular secretion Vree et al, 1980, Vree et al, 1981a. The parent drug SDM is excreted mainly by glomerular filtration.…”

“…In man, sulphadimidine is mainly metabolized via the acetylation-deacetylation pathway, and it is excreted t o a minor extent as parent drug by the kidneys Vree, O'Reilly, Hekster, Damsma & Van der Kleijn, 1980;Vree, Hekster, Damsma, Tijhuis & Friesen, 1981a). The N4-acetylsulphadimidine is predominantly excreted via active tubular secretion (Vree et al, 1981a). Both pathways in the elimination of sulphadimidine may be dependent on age.…”

Effect of intra‐articular glucocorticoids on the disposition of sulphadimidine in chronic osteoarthritis patients.

“…Both glomerular filtration and tubular reabsorption are known to be important in the excretion of sulphadimidine (Vree et al, 1981), and hence the observed increase in renal clearance may be attributed to an enhanced glomerular filtration rate and/or to reduced tubular reabsorption of the drug.…”

Dose dependent disposition of sulphadimidine and of its N4‐acetyl and hydroxy metabolites in plasma and milk of dairy cows

“…The N,-SDM is eliminated by tubular secretion, and hydroxylation of SDM is in man a minor elimination pathway (14,16,18). Hence traces of sulphonamides in edible tissues will not cause adverse reactions in man, because the residence time in man is very short.…”

“…Sulphadimidine was purchased from Sigma; N,-acetylsulphadimidine (N4-SDM), 6-hydroxymethy1-4-methylpyrimidine (SCH2-OH) and 5-hydroxy-4,6-dimethyl-pyrimidine (SOH) were synthesized or isolated according to Vree et al (14,15,17,18). The molecular structures of these four compounds are presented in Fig.…”