首页|Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review

Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review

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  • NSTL
  • Elsevier
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.

VariationFasted and fed statePhysiologyPediatrics and geriatricsDiseasesDrug formulation

Vinarov, Zahari、Abdallah, Mohammad、Agundez, Jose 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、Augustijns, Patrick

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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Drug Delivery & Disposit, Gasthuisberg O&N

Monash Univ, Monash Inst Pharmaceut Sci, Drug Delivery Disposit & Dynam, Parkville, Vic, Australia

Inst Salud Carlos III, Univ Inst Mol Pathol Biomarkers, UEx ARADyAL, Caceres, Spain

Erasmus MC, Dept Hosp Pharm, Univ Med Ctr Rotterdam, Rotterdam, Netherlands

UCL, UCL Sch Pharm, London, England

Janssen Res & Dev, Pharmaceut Sci, Beerse, Belgium

Nottingham Univ Hosp NHS Trust, NIHR Nottingham Biomed Res Ctr BRC, Nottingham, England

Univ Coll Cork, Sch Pharm, Cavanagh Pharm Bldg, Cork, Ireland

Ernst Moritz Arndt Univ Greifswald, Ctr Drug Absorpt & Transport, Dept Biopharmaceut & Pharmaceut

Maastricht Univ, Dept Internal Med, Div Gastroenterol Hepatol, NUTRIM,Med Ctr, Maastricht

AbbVie Deutschland GmbH & Co KG, NCE Formulat Sci, Ludwigshafen, Germany

Katholieke Univ Leuven, Dept Chron Dis & Metab, Clin & Expt Endocrinol, Leuven, Belgium

Janssen Res & Dev, Clin Pharmacol & Pharmacometr, Spring House, PA USA

Natl & Kapodistrian Univ Athens, Sch Hlth Sci, Dept Pharm, Athens, Greece

Katholieke Univ Leuven, Translat Res Ctr Gastrointestinal Disorders TARGI, Dept Chron Dis Metab &

Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci SIPBS, Glasgow, Lanark, Scotland

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2021

10.1016/j.ejps.2021.105812

European journal of pharmaceutical sciences

European journal of pharmaceutical sciences

ISTP
ISSN：0928-0987
年,卷(期)：2021.162
  • 57
  • 398