Exploring Strategies For Selecting Blood Sampling Points In PK-related Research On Pharmacokinetic Data Modeling

In the research of pharmacokinetics,accurate estimation of PK parameters is of great significance,especially in clinical trial research,where individual PK parameters are required to adjust the dose.Intensive sampling will bring pain to patients,reduce compliance,and increase costs.Therefore,we need to improve experimental design,establish models,and accurately estimate PK parameters,so as to guide clinical practice and achieve sampling optimization.In this paper,based on population pharmacokinetics,the nonlinear mixed effects model is combined with the PK model to estimate the model population parameters,and the population pharmacokinetic parameters are combined with the Bayesian feedback method to estimate the individual parameters.An estimated parameter-oriented population pharmacokinetics establishes a sampling optimization plan,as follows:First,it briefly introduces the pharmacokinetic model of intravenous blood injection administration,the principle of Monte Carlo simulation and its importance in clinical trials,the sampling optimization of D optimization method in clinical trials,and the population pharmacokinetics.The principle and application of dynamic nonlinear mixed effects model.Secondly,using R statistical software,introducing population pharmacokinetics(PPK),and simulating the data of subjects with a computer,establishing a nonlinear mixed-effect two-compartment model,performing statistical data analysis,and determining random effects and fixed effects Parameter,get a good model estimation effect.Then,the parameters of the nonlinear mixed-effect model and the Bayesian feedback method are used to obtain the optimized sampling points.Through the one-room model,it is verified that the method can obtain reasonable individual parameter effects in the case of sparse sampling points.And using Win Non Lin software based on the real blood drug concentration data of the subjects,the optimized blood sampling point and the original blood sampling point were used to calculate the main PK parameters,and the effect of the parameters under different numbers of blood sampling points was compared to verify that the method can obtain Good results.Finally,a population pharmacokinetic experiment design optimization method based on estimating model parameters is proposed.Then,based on the PopED package in R language,the method is validated through an example.