TY - JOUR
T1 - Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics
T2 - An UNGAP review
AU - Vinarov, Zahari
AU - Abdallah, Mohammad
AU - Agundez, José A.G.
AU - Allegaert, Karel
AU - Basit, Abdul W.
AU - Braeckmans, Marlies
AU - Ceulemans, Jens
AU - Corsetti, Maura
AU - Griffin, Brendan T.
AU - Grimm, Michael
AU - Keszthelyi, Daniel
AU - Koziolek, Mirko
AU - Madla, Christine M.
AU - Matthys, Christophe
AU - McCoubrey, Laura E.
AU - Mitra, Amitava
AU - Reppas, Christos
AU - Stappaerts, Jef
AU - Steenackers, Nele
AU - Trevaskis, Natalie L.
AU - Vanuytsel, Tim
AU - Vertzoni, Maria
AU - Weitschies, Werner
AU - Wilson, Clive
AU - Augustijns, Patrick
N1 - Funding Information:
This article is based upon work from COST Action UNGAP (CA16205), supported by COST (European Cooperation in Science and Technology), funded by the Horizon 2020 Framework Programme of the European Union.
Publisher Copyright:
© 2021 The Authors
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103697111&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2021.105812
DO - 10.1016/j.ejps.2021.105812
M3 - Article
C2 - 33753215
AN - SCOPUS:85103697111
SN - 0928-0987
VL - 162
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
M1 - 105812
ER -