Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review

Tools

Stillhart, Cordula and Vučićević, Katarina and Augustijns, Patrick and Basit, Abdul W. and Batchelor, Hannah and Flanagan, Talia R. and Gesquiere, Ina and Greupink, Rick and Keszthelyi, Daniel and Koskinen, Mikko and Madla, Christine M. and Matthys, Christophe and Miljuš, Goran and Mooij, Miriam G. and Parrott, Neil and Ungell, Anna Lena and de Wildt, Saskia N. and Orlu, Mine and Klein, Sandra and Müllertz, Anette (2020) Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review. European Journal of Pharmaceutical Sciences, 147. 105280. ISSN 0928-0987 (https://doi.org/10.1016/j.ejps.2020.105280)

[thumbnail of Stillhart-etal-EJPS_2020-Impact-of-gastrointestinal-physiology-on-drug-absorption-in-special-populations]
Preview
 Text. Filename: Stillhart_etal_EJPS_2020_Impact_of_gastrointestinal_physiology_on_drug_absorption_in_special_populations.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo
Download (3MB)| Preview

Abstract

The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.

ORCID iDs

Stillhart, Cordula, Vučićević, Katarina, Augustijns, Patrick, Basit, Abdul W., Batchelor, Hannah ORCID logoORCID: https://orcid.org/0000-0002-8729-9951, Flanagan, Talia R., Gesquiere, Ina, Greupink, Rick, Keszthelyi, Daniel, Koskinen, Mikko, Madla, Christine M., Matthys, Christophe, Miljuš, Goran, Mooij, Miriam G., Parrott, Neil, Ungell, Anna Lena, de Wildt, Saskia N., Orlu, Mine, Klein, Sandra and Müllertz, Anette;
CORE (COnnecting REpositories)