Disposition decomposition analysis

This is sufficient in dealing with the important input-response relationship, but does not enable the effect of specific disposition changes to be considered. The disposition decomposition analysis (DDA) methodology overcomes this problem. DDA is based on a most fnndamental principle of dividing the disposition into two fundamental components namely, an elimination component and a distribution component (Figure 16.3). 

Traditionally, distribution kinetics has been described in terms of volume of distribution parameters (V and K,s) and structure-specific distribution parameters, e.g., the k 2, 21 parameters of the two-compartment model. LSA offers a less-structured alternative that considers the net effect of the distribution kinetics based on the disposition decomposition analysis. For example, the partition/distribution properties of a drag may be expressed in terms of the affinity of the drag molecules to a kinetic space expressed as the MRT in the kinetic space. Accordingly, it is meaningful to consider ratios of MRTs for two kinetic spaces as a metric for the relative affinity. Thus, residence time coefficients (RTC) similar to a partition coefficient may be defined Residence Time Coefficient The residence time coefficient RTC for the distribution of a drug in two kinetic spaces is the ratio of the MRT of the drug in the two kinetic spaces. It is readily shown thaC ... 

System analysis techniques have been used to generate input functions for PB-PK models. Oral administration of carbon tetrachloride in different vehicles was successfully described by absorption input functions obtained by deconvolution and disposition decomposition methods [25,26],... 

P. Veng-Pedersen, Theorems and implications of a model independent elimination/distri-bution function decomposition of linear and some nonlinear drug dispositions. I. Derivations and theoretical analysis. / Pharmacokinet Biopharm 12 627-648 (1984). 

Richard, 1., Cardot, J. M., and Godbillon, J., Stable isotope methodology for studying the performance of metoprolol Oros tablets in comparison to conventional and slow release formulations, Eur. J. Drug Metab. Pharmacokinet., 19 375-380, 1994. Veng-Pedersen, R, Theorems and implications of a model independent elimina-tion/distribution function decomposition of linear and some nonlinear drug dispositions. 1. Derivations and theoretical analysis, J. Pharmacokinet. Biopharm., 12 627-648, 1984. 

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