6th EUFEPS Talks
We want to invite you to the 6th EUFEPS Talks on August 30, 2021 at 4 pm CEST.
Prof. Panos Macheras (Department of Pharmacy, University of Athens, PharmaInformatics Unit, Research Center ATHENA, Athens, Greece), will give a talk with the title: "Drugs are Absorbed in Finite Time: A New Era in Biopharmaceutical Sciences".
A registration is needed for this event. Please use the following link: https://zoom.us/meeting/register/tJcpceqgqD0tH9Z4UHaA5gC2jcxv4jswn_YX. After the regristration you will receive an E-Mail with the log-in details.
From the early days of Pharmacokinetics (1) drug absorption was modeled as a first-order process implying an infinite time for drug absorption. According to the current scientific knowledge and common wisdom, drugs are absorbed passively in finite time.
The concept of “finite time” of absorption has been used in various Physiologically Based Pharmacokinetic (PBPK) models. However, the formal development of Physiologically Based Finite Time Pharmacokinetic (PBFTPK) models was published recently (2-4). The PBFTPK models were built on two principles: i) drugs are absorbed passively for a finite period of time, τ and ii) time absorption constrains linked with the gastrointestinal transit times of drug in the stomach, the small intestines and the colon were applied. Zero- or first-order input is used for the (PBFTPK)0 and (PBFTPK)1 models, respectively. The (PBFTPK)0 models were developed by coupling the drug properties solubility and permeability of the Biopharmaceutic Classification System with the kinetics of drug uptake under sink conditions. The (PBFTPK)1 models rely on first-order drug absorption which is terminated at time τ (5) when the drug either passes beyond the absorptive sites or no more soluble drug is available for absorption.
Simulations based on the (PBFTPK)0 and (PBFTPK)1 models will be used; the generated C, t curves will be discussed in terms of the “finite time” absorption concept. Special emphasis will be given to the elimination phase which operates beyond time τ. The novel meaning of the bioavailability/bioequivalence parameters Cmax, tmax, AUC and the relevant implications will be discussed in the light of the “finite time” absorption concept. A short description and some examples for the use of “PBFTPKsoftware” for fitting purposes will be also presented. Future applications of the “finite time” of absorption concept in drug development and research will be highlighted.
F. Dost, Der Blutspiegel - Kinetic der Konzentrationsabläufe in der Kreislaufflüssigkeit (1953)
Macheras, On an unphysical hypothesis of Bateman equation and its implications for pharmacokinetics. Pharmaceutical Research. 36:94 (2019)
Macheras, P. Chryssafidis. Revising Pharmacokinetics of Oral Drug Absorption: I Models Based on Biopharmaceutical/Physiological and Finite Absorption Time Concepts. Pharmaceutical Research 37, 187 (2020). Erratum: Pharm Res 37, 206 (2020).
Chryssafidis, A, Tsekouras, P. Macheras. Revising Pharmacokinetics of Oral Drug Absorption: II Bioavailability-Bioequivalence considerations Pharmaceutical Research. In press.
Sugano . Lost in modelling and simulation? ADMET DMPK. 2021;9(2):75–109.