Abstract:

The infinite time of oral drug absorption was conceived from the first day of the birth of pharmacokinetics when H. Dost introduced the term pharmacokinetics in his book published in 1953. He adopted the function developed by H. Bateman back in 1908 for the decay of the nuclei isotopes to describe oral drug absorption as a first-order process. We unveiled this false hypothesis relying on common wisdom i.e. drugs are absorbed in finite time. This false assumption had dramatic effects on the evolution of oral pharmacokinetics but most importantly on the bioavailability and bioequivalence concepts and metrics. This work focuses on the finite absorption time (FAT) concept, the relevant Physiologically Based Finite Time (PBFTPK) models developed and their applications in oral pharmacokinetics, bioavailability and bioequivalence. The crux of the matter is that drug absorption from the gastrointestinal tract takes place under sink conditions because of the high blood flow rate in the vena cava. The termination of oral, pulmonary and intranasal drug absorption at a specific time point, calls for regulatory changes in bioavailability and bioequivalence studies in terms of the study design and metrics used for the bioequivalence assessment.