Pharmacokinetics and mechanism of renal excretion of short acting sulphonamides and N4-acetylsulphonamide derivatives in man. Structural requirements of sulphonamides for active tubular secretion

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%.