Time-dependent, plasma-sulfate-independent kinetics of salicylamide in dogs (original) (raw)

The mechanisms of the dose-dependent elimination kinetics of salicylamide in dogs were examined. Salicylamide was infused continuously over three consecutive 90-rain periods. The rates of infusion during Periods I and IH were the same. During Period H the infusion rate was 2.5-fold higher. Plasma concentrations of inorganic sulfate were kept constant by the administration of exogenous sulfate. The plasma concentrations of salicylamide, which reached steady state during Period I but not during H or III, were twice as high at the end of Period IIl than those at the end of Period L Typical Michaelis-Menten kinetics do not explain these results. When salicylamide was given as 40 mg/kg single oral dose, clearance of an intravenous tracer dose of radiolabeled salicylamide was greatly reduced within 10 min but returned to baseline values by 240 rain after the oral dose, despite persistently low plasma concentrations of inorganic sulfate. Therefore, doseand time-dependent factors other than Michaelis-Menten kinetics, depletion of inorganic sulfate concentrations, and rate limitation of supply of "active sulfate" from plasma inorganic sulfate stores produce the dose-and time-dependent kinetics of salieylamide in the dog. Product inhibition of salicylamide sulfoeonjugation remains a possible explanation.