Supervisors info:
Παναγιώτης Μαχαίρας, Ομότιμος Καθηγητής, Τμήμα Φαρμακευτικής ΕΚΠΑ
Παρασκευάς Δάλλας, Αναπληρωτής Καθηγητής, Τμήμα Φαρμακευτικής ΕΚΠΑ
Δημήτριος Ρέκκας, Καθηγητής, Τμήμα Φαρμακευτικής ΕΚΠΑ
Summary:
The concept of infinite time in oral drug absorption, rooted in early pharmacokinetics, was initially formulated by H. Dost in 1953, drawing on H. Bateman's 1908 function for nuclear isotope decay. This premise, assuming first-order kinetics, proved to be physiologically unsound over the decades, significantly impacting the evolution of oral pharmacokinetics, bioavailability, and bioequivalence metrics. The Finite Absorption Time (F.A.T.) concept emerged as a corrective paradigm, leading to the development of Physiologically Based Finite Time Pharmacokinetic (PBFTPK) models. This thesis delves into the theoretical underpinnings of the F.A.T. concept, exploring its application to several BCS Class I biowaiver drugs. By examining and classifying drugs based on F.A.T. values, this study sheds light on its potential applications in drug absorption research and regulatory guidelines. The findings underscore the F.A.T. concept's relevance in assessing drug input rates, stochastic mean absorption time calculations, population analyses, in vitro-in vivo correlations, and bioequivalence guidelines.
Furthermore, this research endeavors to extend the understanding of drug dissolution dynamics through the development of a Temporal Biopharmaceutic Classification System (T-BCS). The T-BCS links the Finite Dissolution Time (F.D.T.) and Mean Dissolution Time (M.D.T.) for Class I/III drugs and Mean Dissolution Time for saturation (M.D.T.s.) for Class II/IV drugs. Through graphical estimation or fitting dissolution models to experimental data, coupled with the dose-to-solubility ratio (q) normalized by the actual volume of dissolution medium (900 mL), this framework provides insights into drug behavior across different dissolution themes. This integrated approach not only enhances our understanding of drug absorption kinetics but also offers a systematic framework for classifying drugs based on dissolution dynamics, thus contributing to the refinement of drug development and regulatory practices.
Keywords:
Drug Classification, Biowaivers, Finite Absorption Time, Dissolution
