In vivo evaluation of the Michaelis-Menten constant for a medium extraction ratio drug: application to cinromide in the rhesus monkey.

The dose-dependent nonlinearity of the clearance of cinromide, a medium extraction ratio drug, has been established in two monkeys. Special problems encountered in evaluation of nonlinearity of such drugs were resolved by the experimental design: cinromide was infused to steady state via the portal vein. A linearized form of the Michaelis-Menten equation was used to determine Vmax and Km. In addition, cinromide was administered to one of the monkeys via a femoral vein to verify the overestimation of Km by administration at a peripheral venous site.