Analytical approximations of sensitivities of steady state predictions to errors in parameter estimation: II. Michaelis-Menten kinetics.

Linear sensitivity theory is used to estimate the reliability of predictions of the minimum and maximum concentrations at steady state in the Michaelis-Menten model with i.v. bolus. The dependence of the relative errors in the predictions on the errors in the pharmacokinetic parameters is derived in an analytical form. It is shown that the quality of the predictions is not equally sensitive to all errors in parameters, and that the sensitivity factors vary with the degree of saturation of the system. An example of application for a drug, such as phenytoin, is discussed. It is suggested that sensitivity analysis may be useful in design of pharmacokinetic experiments aimed at the control of steady state levels for drugs with Michaelis-Menten kinetics.