Dose-Dependent Kinetics of Probenecid in Rhesus Monkeys – Infusion Studies

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Abstract
14 infusion studies to steady state with probenecid were carried out in 2 monkeys. Plasma clearance decreased with increasing rate of infusion. The urinary excretion data showed a decrease in the fraction of the dose excreted as probenecid conjugate, an increase in the total N-depropyl metabolites, and no change in the 2-hydroxy metabolites with increasing probenecid dose. Pooled Michaelis-Menten constants for probenecid metabolism were estimated from a plot of the linearized Michaelis-Menten equation using infusion rates of probenecid versus the plasma clearances of the drug.

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