CXT-MAIN: a software package for determination of the analytical form of the pharmacokinetic system weighting...

A new procedure specific for the determination of the analytical form of the model weighting function of a complex multicomponent pharmacokinetic system with or without a shunt and time delays is described. The procedure is based on the theory of linear dynamic systems and on a circulatory pharmacokinetic model of the living body. The model transfer function of the system under study was obtained by the frequency response method in the form of the ratio of two frequency dependent polynomials. Subsequently, the technique of the partial fraction inversion was employed to determine the analytical form of the model weighting function. Two examples from bioavailability studies in pharmacokinetics are given. The first example presents two estimates of the model weighting function of a pharmacokinetic system obtained by the new procedure and by a polyexponential deconvolution method. To compare these results, two models of the measured system output were determined using the two estimates of the model weighting function, the actual system input and a convolution method. The model weighting function obtained by the new procedure yielded a better model approximation of the output data than that obtained by the polyexponential deconvolution method. The second example, using the new procedure, presents the determination of the model weighting function of such a system that the deconvolution methods, commonly used in pharmacokinetics, cannot be applied to.