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Piekarski S., Kiełczyński P., Szalewski M., Rewekant M.♦, Computer-based simulation of plasma concentration time-profiles of drug in nonlinear two-compartment model,
COMPUTER ASSISTED METHODS IN ENGINEERING AND SCIENCE, ISSN: 2299-3649, Vol.20, pp.279-288, 2013 Abstract:
The main interest of pharmacokinetics is the study of the fate of drugs in the living organism. This work proposes the system of the conservation laws that describes time-dependent concentrations of a drug, after a single intravenous administration. Compared with others, the proposed model considers both free and protein-bound drug concentrations at the same time. Plasma protein binding captured in the model enters the nonlinearity arising from the Guldberg-Waage law. According to our best knowledge, the analytical solution for our system does not exist. Our model allows the calculation of the free and bound-drug protein concentrations at any time point and at any dose after single intravenous bolus dose administration. In order to compare the empirical with simulated data, a numerical approach has been proposed. On the basis of published experimental data the model validation has been carried out. The goodness of fit was satisfactory (R2 = 0.99) and the experimental and simulated AUC (area under the curve) values, as the measure of the bioavailability of drug, were similar (150 M/hxh−1). The preliminary assessment of the model credibility was positive and encouraged further studies.
Keywords:
Evolution equations, non-linear model, drug protein binding Affiliations:
| Piekarski S. | - | IPPT PAN | | Kiełczyński P. | - | IPPT PAN | | Szalewski M. | - | IPPT PAN | | Rewekant M. | - | Medical University of Warsaw (PL) |
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