Comparative pharmacokinetic studies of sulphonamides

Abstract

In species-dependent pharmacokinetics, there are 3 main variables: the structure of the drug, the mechanism and route of metab., and renal excretion. When the drug is administered orally, the structure and characteristics of the gastrointestinal tract are an addnl. factor which may dominate the overall pharmacokinetic behavior. Sulfonamides are metabolized by acetylation-deacetylation reactions and by hydroxylation. Hydroxylation is possible at different positions in the N1-substituent group. The ratio between acetylation and hydroxylation depends on the structure of the sulfonamide and the species. Renal function, as expressed by inulin or creatinine clearance, is almost independent of the species and is related to the body wt. The renal excretion mechanisms of sulfonamides and their metabolites are governed by the mol. structure and kidney architecture, but are not affected by the test animal species. [on SciFinder(R)]