Modelling Of Pharmacokinetics And Pharmacodynamics Of Aspirin, Simulation Of The Administration With Different Timing And Dose, Simulation Of The Administration In Situation Of Poor Compliance.

Objectives:The aims of these serial studies were to set the PK-PD mathematical model of aspirin so as to describe the progress of the pharmacokinetics and pharmcodynamics of aspirin kinetically in all respect, to analyze the effect of administration with different timing and dose, to analyze the result of administration in one poor-compliance pattern.Methods:1. Based on the theory of pharmacokinetics,pharmacodynamics and modelling of aspirin in the references, we wrote programmes to set up mathematical model of pharmacokinetics-pharmacodynamics of aspirin using MATHEMATICA 4.0 software in computer.2. We performed simulations of two months administration of aspirin with different doses(50.75.100.150.200.300.400.500mg per day) and timing(Qod,Qd,Bid). Then we calculated the pharmacodynamics parameter of all the simulations, analyzed the differences of anti-platelet aggregation effect between different administration methods.3. We set up a model to simulate randomized non-compliance administration. Then we performed simulations of one year administration of aspirin with different doses(50.75.100.160.200.300.400.500mg per day) and coefficient of variation (from 10% to 100% with the step of 10%).Then we calculated the pharmacodynamics parameter of all the simulations, analyzed the differences of anti-platelet aggregation effect between different simulations. Results:1. We set up a aspirin pharmacokinetics-pharmacodynamics mathematical model successfully, it described the progress of pharmacology of aspirin perfectly.2. In simulation of different doses and timing, the bigger the dose, the earlier and stronger the effect. We calculated the area under the effect-time curve of every administration as a effect marker, and made effect-dose curves for three administration methods. The curvature of the curve was increasing as the frequency of administration was decreasing. For every curve, when dose was larger than 300mg per day,the curvature tended to be mild.3. In simulation of non-compliance administration, The duration of inefficacy increased as the CV increased or as the dose decreased. When dose was larger than 300mg per day, the effect of dose or CV on the duration of inefficacy tended to be small.Conclusions:1. To some extent there is a dose-effect relationship in the therapy of aspirin, Large dose was more powerful and effected quickly, but this effect tended to be small when dose was larger than 200-300mg per day.2. The effect/dose ratio was highest in the group administrated twice a day. The effect was more quickly and stably in this group.3. Administrating with large dose on alternate day was as effective as administrating with low dose once a day.4. Considering both non-compliance and side effect,200-300mg is the most optimal dose for aspirin.5. Aspirin was a forgiven drug to some extent.