Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics : an UNGAP review
Vinarov, Zahari and Abdallah, Mohammad and Agundez, José A.G. and Allegaert, Karel and Basit, Abdul W. and Braeckmans, Marlies and Ceulemans, Jens and Corsetti, Maura and Griffin, Brendan T. and Grimm, Michael and Keszthelyi, Daniel and Koziolek, Mirko and Madla, Christine M. and Matthys, Christophe and McCoubrey, Laura E. and Mitra, Amitava and Reppas, Christos and Stappaerts, Jef and Steenackers, Nele and Trevaskis, Natalie L. and Vanuytsel, Tim and Vertzoni, Maria and Weitschies, Werner and Wilson, Clive and Augustijns, Patrick (2021) Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics : an UNGAP review. European Journal of Pharmaceutical Sciences, 162. 105812. ISSN 0928-0987 (https://doi.org/10.1016/j.ejps.2021.105812)
Preview |
Text.
Filename: Vinarov_etal_EJPS_2021_Impact_of_gastrointestinal_tract_variability_on_oral_drug_absorption.pdf
Final Published Version License: Download (5MB)| Preview |
Abstract
The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. The source of variability can be traced back to interindividual variability in physiology, differences in special populations (age- and disease-dependent), drug and formulation properties, or food-drug interactions. Clinical evidence for the impact of some of these factors on drug pharmacokinetic variability is mounting: e.g. gastric pH and emptying time, small intestinal fluid properties, differences in pediatrics and the elderly, and surgical changes in gastrointestinal anatomy. However, the link of colonic factors variability (transit time, fluid composition, microbiome), sex differences (male vs. female) and gut-related diseases (chronic constipation, anorexia and cachexia) to drug absorption variability has not been firmly established yet. At the same time, a way to decrease oral drug pharmacokinetic variability is provided by the pharmaceutical industry: clinical evidence suggests that formulation approaches employed during drug development can decrease the variability in oral exposure. This review outlines the main drivers of oral drug exposure variability and potential approaches to overcome them, while highlighting existing knowledge gaps and guiding future studies in this area.
ORCID iDs
Vinarov, Zahari, Abdallah, Mohammad, Agundez, José A.G., Allegaert, Karel, Basit, Abdul W., Braeckmans, Marlies, Ceulemans, Jens, Corsetti, Maura, Griffin, Brendan T., Grimm, Michael, Keszthelyi, Daniel, Koziolek, Mirko, Madla, Christine M., Matthys, Christophe, McCoubrey, Laura E., Mitra, Amitava, Reppas, Christos, Stappaerts, Jef, Steenackers, Nele, Trevaskis, Natalie L., Vanuytsel, Tim, Vertzoni, Maria, Weitschies, Werner, Wilson, Clive ORCID: https://orcid.org/0000-0002-4211-7907 and Augustijns, Patrick;-
-
Item type: Article ID code: 76207 Dates: DateEvent1 July 2021Published20 March 2021Published Online16 March 2021AcceptedSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 22 Apr 2021 15:52 Last modified: 02 Oct 2024 12:19 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/76207