Pharmacokinetics of sulfaethidole in the rat: nonlinear multicompartment solution

Sulfaethidole distribution and elimination in the rat was studied over a 90-fold dose range. This experimental design produced marked nonlinearity in the binding of sulfaethidole to proteins in both interstitial fluid an plasma. Using a multicompartmental model consisting of binding of sulfaethidole to plasma and interstitial fluid proteins, sulfaethidole distribution in the body could be simulated. Urinary and biliary elimination of sulfaethidole depended on the unbound drug mass in the plasma and urine flow. The results confirm the central role of the unbound species in the distribution and elimination of drugs with marked binding to plasma proteins.