Michaelis-Menten elimination kinetics: areas under curves, steady-state concentrations, and clearances for compartment models with different types of input.

Abstract

For single bolus administration, intermittent bolus administrations to steady-state, a single dose as a zero order input, intermittent zero order inputs to steady-state, and continuous zero order input to steady-state, and for both simple Michaelis-Menten elimination and parallel Michaelis-Menten and first order elimination, the appropriate equations are given for the areas, AUC 0-oo or AUC 0-tau, steady-state concentrations, and clearances. Some 20 new equations have been derived. For the case of first order input and Michaelis-Menten elimination, no solution is given but the effect of input rate on systemic availability is reported following some numerical integrations. The effect of slow input in reducing systemic bioavailability when Michaelis-Menten elimination kinetics are operative is stressed and the implications of this in the field of sustained-release medication mentioned.