Determination of the in vivo Km and Vmax of a drug with tracer studies.

A method is described for determining the in vivo Km and Vmax values for a drug, utilizing a variant of the Michaelis-Menten equation and the elimination-rate constants of tracer doses of the drug administered at two different serum concentration values. The new method is the most accurate yet devised; unlike older methods, it is dependent on assumptions that generally are true and can be validated empirically. Application of the method is demonstrated by a study of phenytoin in humans.