Kinetic nonparametric

Unadkat, J.D. Bartha, F. Sheiner, L.B. Simultaneous modeling of pharmacokinetics and pharmacodynamics with nonparametric kinetic and dynamic models. Clin. Pharmacol. Ther. 1986, 40 (1), 86-93. 

Others have modeled the biophase using systems (24,25), semiparametric models (50), and nonparametric (15) models to account for the temporal displacement of the effect curve relative to Q,. The two other elements, biosensor and transduction kinetics, in PD modehng can also be employed to account for effect curve temporal displacement. These other two areas are covered in other chapters of this book. 

A modification of the forcing function approach makes use of linear systems analysis for individual tissue compartments. Parametric or nonparametric fnnctions are fitted to observed blood drug concentration-time data, and then combined with tissue drug concentration-time measurements deconvolved to obtain a disposition fnnction for drug kinetics in the tissue. From the tissue disposition function, certain parameters for blood flow-limited organ models can be obtained. 

In contrast to other modeling approaches, the disposition decomposition technique enables the elimination kinetics to be isolated and determined nonparametrically without the need for a specific structured modeling of the distribution kinetics. Such objective determination of the nonlinear elimination kinetics is of significant value in the areas of nonlinear drug level predictions and absorption evaluations. Moreover, the nonparametric determination provides a useful visualization of the nonlinear elimination kinetics that may be quite helpful in determining the mechanism of the elimination process. 

Another advanced analysis method applicable to the SSITKA studies makes use of convolution, well known for linear systems. Making use of linear convolution in parametric and nonparametric kinetic analyses, provides increased accuracy for the determination of the kinetic parameters... 

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