Implementation of an approximate input forcing function for modelling single tissues in the Open Pharmacology Suite

Objectives: The PK-Sim®software is used for the development of whole-body physiologically-based pharmacokinetic (PBPK) models. During model development parameters for drug disposition must be provided, often sourced from in vivo/in vitro experiments. If these parameters are influential, misspecification in a single organ can impact the entire PBPK model. Through development of single-tissue models, initial estimates for influential parameters […]

Optimal design for determination of AUC with no prior pharmacokinetic knowledge

Objectives: To develop a method for choosing sample intervals that provide accurate estimates of area under the concentration-time curve (AUC) when using the log trapezoidal method. The developed method will only require single individual or mean pooled concentration data and will not require prior pharmacokinetic knowledge for the drug of interest, as in the case […]

Comparison of Non-Compartmental and Mixed Effect Modelling Methods for Establishing Bioequivalence for the Case of Two Compartment Kinetics and Censored Concentrations

Non-compartmental analysis (NCA) is regarded as the standard for establishing bioequivalence, despite its limitations and the existence of alternative methods such as non-linear mixed effects modelling (NLMEM). Comparisons of NCA and NLMEM in bioequivalence testing have been limited to drugs with one-compartment kinetics and have included a large number of different approaches. A simulation tool […]