Dose-dependent kinetics of probenecid in rhesus monkeys-intravenous bolus studies

14 bolus studies with probenecid in a dose range of 8.2--164 mg/kg were carried out in 3 monkeys. The protein binding of probenecid in the plasma was studied by an ultracentrifugation method. Plasma clearances of both total and unbound probenecid decreased with increasing doses, while the volume of distribution and fraction of metabolites excreted in the urine remained constant. The urinary excretion rates of probenecid and it metabolites were measured in a bladder-catheterized monkey and were found to be urine flow dependent. Since the rate-limiting step for the excretion of the metabolites did not depend on the formation rate only, biliary recycling was speculated.