Determination of the Acetylator Phenotype and Pharmacokinetics of Some Sulphonamides in Man

Abstract

The pharmacokinetics of sulphamethizole, sulphamethoxazole, sulphadiazine, sulphapyridine and sulphadimidine have been studied in man. Renal clearance values of the metabolite N₄-acetylsulphonamide are 6 to 20 times higher than those of the corresponding parent compound. The renal clearance of sulphonamides is dependent on the urine flow. N₄-Acetylsulphonamide concentration-time profiles for plasma and urine have been constructed for the sulphonamides. The percentage N₄-acetylsulphonamide-time profiles for plasma are excellent tools for establishing the acetylator phenotype, while those constructed from urine samples are less useful. Evidence is obtained that sulphadimidine is metabolically processed by 2 different isoenzymes, while sulphadiazine, sulphapyridine and sulphamethoxazole are processed by I acetylating isoenzyme. Sulphamethizole is acetylated to very little extent.