Simultaneous modeling of pharmacokinetics and pharmacodynamics: an improved algorithm

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Abstract
An algorithm and computer program is presented that fits a largely non-parametric model to pharmacokinetic (PK) and pharmacodynamic (PD) data; it is an extension of a recently proposed approach. A PK model relates dose to plasma concentrations (Cp), a link model relates plasma concentrations to the concentration in the effect site (Ce), a PD model relates Ce to the effect. Both the PK and the PD model are non-parametric, but the link model is parametric. The extension presented here allows modeling of PK/PD data arising from non-steady-state experiments after arbitrary dosage. In addition, several data sets from the same individual (or from different individuals) can now be analyzed simultaneously, assuming the same link model for all, but allowing either all the PD models to be the same, or all to be different.