Physiologically based pharmacokinetic (PBPK) models are mathematical models, which, are parameterized by considering the physiology of an individual. To circumvent the overall model complexity of whole-body PBPK models, the lumping of tissue compartments has been proposed in literatures. The resulting PBPK model which inherits physiological attributes of the whole-body PBPK models has been defined as the minimal-PBPK model. The purpose of this study is to develop a minimal-PBPK model for intravenously administered insulin by considering both the blood flow (perfusion) and permeability of the cell membrane as a structural model for population analysis. Together with this, a residual error model, which represents the statistical part of the model was evaluated.
Upon completion, participant will be able to apply the framework of minimal physiologically based pharmacokinetics for population analysis for generating physiologically relevant pharmacokinetic parameters which are easily interpreted as compared to compartmental modeling.
Upon completion, participant will be able to perform population parameter estimation by using the stochastic approximation expectation maximization (SAEM) algorithm, in conjunction, with Gauss-Newton algorithm with Levenberg-Hartley modification (for estimation of initial estimates) to overcome the challenge of small sample size used in a study.
Upon completion, participant will be able to estimate the tissue/plasma partition coefficient (Kp) and permeability surface area product (PS) as a fitted parameter for the test population, when only plasma profile is available. These parameters may then be employed into a whole-body PBPK model for further exploratory analysis.