Revising Oral Pharmacokinetics, Bioavailability and Bioequivalence Based on the Finite Absorption Time Concept

This book casts new light on the field of oral drug absorption. It outlines both the concept of the past and the novel concept of Finite Absorption Time (FAT). In addition, the authors explore the correlated need for re-definition of bioavailability, bioequivalence providing a plethora of experimental data. Chapter 1 introduces the work of the first applications at the turn of the 20th century of first-order kinetics in Physics and the Bateman equation based on a model with three radioactive species; this equation was adopted by Dost in 1953 to describe the concentration-time curve of drug absorption after oral administration assuming one-compartment model. Chapter 2 describes the extensive use of first-order kinetics in oral drug absorption phenomena along with the governing role of the absorption rate constant; the last portion of the chapter focuses on the unphysical assumption associated with the use of Bateman equation in pharmacokinetics. The FAT concept is introduced in Chapter 3 using a minimal model of gastrointestinal drug absorption based on passive drug absorption under sink conditions and physiological absorption time limits. The relevant Physiologically Based Finite Time Pharmacokinetic (PBFTPK) models are developed in Chapter 4; the potential of PBFTPK models through detailed simulations is shown, while a variety of experimental data is used to determine the best models and optimum parameter values for the duration of drug's absorption and other kinetic rate constants. Chapter 5 is about the evolution of bioavailability-bioequivalence since early 1960s until the establishment of the bioavailability concept by FDA in 1977. Chapter 6 describes the basics of bioequivalence criteria for the assessment of therapeutic equivalence of generics vs. the innovator's products as well as the problem of the highly variable drugs. Chapter 7 shows that the FAT causes a paradigm shift in oral pharmacokinetics. Explicit relationships are derived for the bioavailable fraction as a function of the model parameters. Chapter 8 shows that a new methodology based on the FAT concept is required for the assessment of bioequivalence.