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

Stillhart, C; Vučićević, K; Augustijns, P; Basit, AW; Batchelor, H; Flanagan, TR; Gesquiere, I; ... Müllertz, A; + view all (2020) Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review. European Journal of Pharmaceutical Sciences , 147 , Article 105280. 10.1016/j.ejps.2020.105280. Green open access

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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.

Type: Article
Title: Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejps.2020.105280
Publisher version: https://doi.org/10.1016/j.ejps.2020.105280
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Oral drug absorption, Special populations, Gastrointestinal tract physiology, Biopharmaceutics, Oral bioavailability
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10093028
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