The Computer Simulation Technology Based On Drug Clinical Trials (cts) Of The Second Chamber Model Analysis

Clinical trial simulation combines the simulation and clinical trials to generate a response for a virtual subject. It can simulate the trial design, human behavior, disease progess and drug behavior by modeling physiopathology and therapy pharmacology of the biosystem. As one part of the modern drug development, CTS effectively solved many practical problems that restrict drug development such as the long term and high cost.Among various models of CTS, as the basic input/output model, pharmacokinetics and pharmacodynamics models are of great importance to analyze the interaction between drug and body.Based on CTS, the influence of parameters on the plasma drug concentration of central compartment and drug effect was analyzed in the two-comparment pharmacokinetic model and Sigmoid Emax pharmacodynamic model by simulating in this thesis. The influence of uncertainty of parameters on the plasma drug concentration was investigated using fuzzy sets and fuzzy logic theory. The main parts of the thesis are as follow:1. The realationship among absorption rate constant, elimination rate constant and the plasma drug concentration characteristics of central compartment in the Dextromethorphan two-comparment pharmacokinetic model with oral administration was investigated by simulating.2. The relationship among dose, parameters and the drug effect in the Dextromethorphan Sigmoid.Emax pharmacodynamic model was investigated by simulating.3. Considering the uncertainty of model parameters, the parameters were presented as fuzzy number and the plasma drug concentration was predicted based on the fuzzy sets theory. The influence of parameters on central compartment plasma drug concentration in the two-compartment model with oral administration was analyzed by calculating fuzzy neartude.4. The two-variable fuzzy adjuster was designed using expected plasma drug concentration as reference to adjust the central compartment plasma drug concentration by altering parameters. The influence of the two-variable fuzzy adjuster on the plasma drug concentration while adjusting model parameters was investigated.The relationship between drug effect and dose and parameters can be clearly observed via simulation.The results which were accordance with clinical trial demonstrated that every individual is of different PK and PD characteristics. It is of great importance to individualized dosage regimen. Fuzzy theory as a powerful tool analyzing the uncertainty of parameters can offer scientific grounds to predict and adjust plasma drug concentration.