| A compartmental model for the absorption and distribution of oral solutions of aspirin has been developed. Compartments for the stomach, duodenum, jejunum ileum, portal system, liver and plasma have been included. This is an improvement over earlier models for drug absorption, in which flow in the gut and the estimation of plasma levels have seldom been combined. Plasma compartment concentrations predicted for rat, dog and man are in agreement with reported aspirin levels.; A technique called modal analysis (Palsson, B. O. and Lightfoot, E. N., J. Theo. Bio., 111: 273 - 302) was used to reduce the number of differential equations in the model and to identify the critical model parameters. This analysis indicated that gastric emptying is theoretically the rate limiting process in absorption for all three species. Dynamics in the plasma compartment were also critical in determining simulation results.; The model has been used to predict the differences between aspirin concentrations in the portal and peripheral veins. Achieving high portal versus peripheral concentrations may be important to the therapeutic success of aspirin as an antiplatelet agent. The ratio of the simulated peak portal compartment concentration to the simulated peak plasma (peripheral) compartment concentration was ten times greater for a dose delivered as a bolus to the jejunum than for a similar dose delivered to the stomach. This result was qualitatively confirmed by experiments in rats. Dosage forms which release aspirin in the jejunum rather than the stomach are therefore postulated to provide more effective antiplatelet activity. |
