Fundamental Pharmacokinetic Behavior of Sulfadimethoxine, Sulfamethoxazole and Their Biotransformed Products in Dogs

Plasma concentration profiles of sulfadimethoxine, sulfamethoxazole and their biotransformed products (N4-acetate and N1-glucuronide) in dogs were determined and their pharmacokinetic parameters were calculated by using a two-compartment open model. The apparent partition coefficients between chloroform and phosphate buffer were also determined. Decline in plasma levels of sulfadimethoxine and sulfamethoxazole was considerably accelerated by N4-acetylation and N1-glucuronidation. The elimination of sulfadimethoxine-N1-glucuronide from plasma was more rapid than that of sulfadimethoxine-N4-acetate, and a similar tendency was observed for sulfamethoxazole and its biotransformed products. N4-Acetylation or N1-glucuronidation of sulfadimethoxine and sulfamethoxazole decreased the lipid solubilities markedly in comparison with those of original sulfonamides.