Disposition of sulfadimethoxine in cattle: Inclusion of protein binding factors in a pharmacokinetic model

Sulfadimethoxine was administered intravenously and orally to four cattle, and plasma and urine samples were collected at various times postdose. Modeling these data with a linear pharmacokinetic model gave unsatisfactory fits, and the data were subsequently fitted to a one-compartment model with saturable protein binding. The saturable protein binding model included the usual linear excretion and elimination processes as well as protein binding parameters. The values obtained in vivo for the binding constant, 5.01 × 10⁴ M⁻¹, and the total protein concentration, 7.89 × 10⁻⁴ M, compared favorably with previously reported in vitro values. These results indicate that protein binding can be successfully included in a pharmacokinetic model.