Modeling in Biopharmaceutics, Pharmacokinetics and Pharmacodynamics Homogeneous and Heterogeneous Approaches

The objectives and scope of this book remain the same as in the first edition: to present the homogeneous and heterogeneous approaches used in the modeling work of biopharmaceutics, pharmacokinetics, and pharmacodynamics. However, in the ensuing ten years from the first publication of the book, significant changes took place in the modeling and simulation work in the field of drug development and research. The prominent drug agencies US FDA and EMA have taken specific steps toward the utility of modeling and simulation in drug development and registration of medicinal products. Moreover, the latest EMA guideline on investigation of bioequivalence introduced several new concepts including alternative possibilities for the clinical design, the statistical analysis, the moiety to be analyzed, and the application of classification of drugs using the biopharmaceutic classification system (BCS) as well as the biopharmaceutic drug disposition classification system (BDDCS). As a result of all these developments, this edition contains two new chapters “Fractional Pharmacokinetics” (Chapter 9) and “Modeling and Simulation in Bioequivalence” (Chapter 10) written by Dr. Aristides Dokoumetzidis and Dr. Vangelis Karalis, respectively. Chapter 9 presents the mathematical formalism based on fractional calculus for the analysis of pharmacokinetics of drugs following anomalous kinetics. Chapter 10 presents an overview of the modeling and simulation methods, which are applied to many areas of bioequivalence assessment. Besides, new material has been added in Chapters 5 and 6 based on recent developments in reaction-limited dissolution models and supersaturated dissolution data as well as the recent advances related to BCS and BDDCS. Also, new sections regarding the time-varying models and analysis of nonlinear mechanisms were also added to Chapters 7 and 13, respectively. Almost all models and procedures were implemented within MATLAB, the commonly used software for numerical analysis purposes.