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

Vinarov, Z; Abdallah, M; Agundez, J; Allegaert, K; Basit, AW; Braeckmans, M; Ceulemans, J; ... Augustijns, P; + view all (2021) Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: an UNGAP review. European Journal of Pharmaceutical Sciences , Article 105812. 10.1016/j.ejps.2021.105812. (In press). Green open access

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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.

Type: Article
Title: Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: an UNGAP review
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejps.2021.105812
Publisher version: https://doi.org/10.1016/j.ejps.2021.105812
Language: English
Additional information: This version is the version of record, available under CC BY licence
Keywords: ADME , Absorption, distribution, metabolism and excretion, AIDS, Acquired immunodeficiency syndrome, AUC, Area under the curve, BCS, Biopharmaceutics classification system, BMI, Body mass index, C(max), Maximum plasma concentration, CD, Cyclodextrin, CETP, Cholesterylester transfer protein, CI, Confidence interval, CIPO, Chronic intestinal pseudoobstruction, CRA, Cannabinoid receptor agonist, CTT, Colon transit times, CV, Coefficient of variance, CYP, Cytochrome P450, D(v50), Median particle size by volume, DAG, Diacylglycerides, DDI, Drug-drug interactions, EHC, Enterohepatic circulation, FDA, U.S. Food and drug administration agency, FFA, Free fatty acids, FaHIF, Fasted state human intestinal fluids, FaSSIF, Fasted state simulated intestinal fluids, GC, Glycocholate, GCDC, Glycochenodeoxycholate, GDC, Glycodeoxycholate, GET, Gastric emptying time, GIT, Gastrointestinal tract, HIV, Human immunodeficiency virus, HPMC, Hydroxypropyl methylcellulose, HPMC-AS, Hydroxypropyl methylcellulose acetate succinate, HPMCP, Hydroxypropyl methylcellulose phtalate, IBD, Inflammatory bowel disease, IMMC, Inter-digestive migrating motor complex, IR, Immediate release, L-DOPA, Levodopa, Lyso-PC, Lyso-phosphatidylcholine, MAG, Monoacylglycerides, MRI, Magnetic resonance imaging, NAPQI, N-acetyl-p-benzoquinone imine, NSAID, Nonsteroidal anti-inflammatory drug, OHM, 1-hydroxy-midazolam, PBPK, Physiologically based pharmacokinetic modelling, PC, Phosphatidylcholine, PD, Pharmacodynamic(s), PEG, Polyethylene glycol, PK, Pharmacokinetic(s), PPI, Proton pump inhibitors, RYGB, Roux-en-Y gastric bypass, SBWC, Small bowel water content, SIBO, Small intestinal bacterial overgrowth, SITT, Small intestinal transit time, TAG, Triacylglycerides, TC, Taurocholate, TCDC, Taurochenodeoxycholate, TDC, Taurodeoxycholate, TKI, Tyrosine kinase inhibitors, UDC, Ursodeoxycholate, UNGAP, European network on understanding gastrointestinal absorption-related processes, VEGF-C, Vascular endothelial growth factor C, t(max), Time to reach maximum plasma concentration, variation, fasted and fed state, physiology, pediatrics and geriatrics, diseases, drug formulation Abbreviations list 5-FU, 5-fluorouracil
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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/10124958
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