ABSTRACT
The concept of sensitivity analysis (SA) has been widely used in the fields of system theory and statistical modeling (1-4). It has been mentioned in connection with the analysis of compartmental systems (5, 6) in a theoretical setting, and applied to a number of chemical (combustion kinetics) and biochemical (metabolism kinetic) studies (7, 8). SA has received inadequate attention in pharmacokinetic (PK) and pharmacodynamic (PD) modeling and its potential has not been fully utilized. Several papers on sensitivity analysis of PK models have appeared recently (9-16), most of them related to physiologically based pharmacokinetic (PBPK) models for risk assessment and analysis of toxic drugs and chemicals. A very limited number of SA studies of the commonly used one-and two-compartment PK models (17) and PK-PD models (18, 19) has been published. The existing research tends to lack formality and comprehensiveness; most of the publications are confined to simple cases of perturbing one or more model parameters, simulating the system and registering the output concentration variations.
