Disposition decomposition analysis for pharmacodynamic modeling of the link compartment.

An approach based on disposition decomposition analysis (DDA) and the hysteresis minimization principle has been developed for pharmacodynamic modeling. It allows calculation of the mean transit time and the ratio of distribution clearance to biophase distribution volume of drug, and determination of the drug concentration-time function at the biophase (Cb(t)). The proposed method extends the DDA approach to drug distribution to a possibly heterogeneous effect compartment of a generalized pharmacokinetic/pharmacodynamic model. The application of this DDA-dynamics method is demonstrated using published data for pancuronium.