4.5.2. Computational algorithms and tools

Common PK–PD models include the linear model, log-linear model, maximum effect model (E_max), sigmoid E_max model, and β-function model. Moreover, the connection mode of PK–PD can be divided into four attributes132. NONMEM is a powerful tool for nonlinear mixed effects modeling and pharmacokinetic and pharmacodynamic data simulation and has been used in the PK–PD study of intranasal and intravenous dexmedetomidine133. In addition, the ANN modeling method can be used to establish a PK–PD prediction model134^,135. These models are more suitable for the study of a single active constituent. In the TCM system, there is a complex relationship between multiple constituents and multiple effects, where the constituents also interact with each other. Therefore, it is necessary to develop models in accordance with the characteristics of TCM.