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

Vinarov, Zahari; Abdallah, Mohammad; Agúndez, José A.G.; Allegaert, Karel; Basit, Abdul W.; Braeckmans, Marlies; Ceulemans, Jens; Corsetti, Maura; Griffin, Brendan T.; Grimm, Michael; Keszthelyi, Dániel; Koziolek, Mirko; Madla, Christine M.; Matthys, Christophe; McCoubrey, Laura E.; Mitra, Amitava; Reppas, Christos; Stappaerts, Jef; Steenackers, Nele; Trevaskis, Natalie L.; Vanuytsel, Tim; Weitschies, Werner; Wilson, Clive G.; Augustijns, Patrick

doi:10.1016/j.ejps.2021.105812

Cited by 179 publications

(128 citation statements)

References 362 publications

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“…The effect of food on drug absorption is one of the major causes of inter-individual variability in drug bioavailability [ 39 , 40 ]. Prospective prediction of FE is important for clinical trial design and dosing regimen prediction, particularly for narrow-therapeutic index drugs.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Food Effect on Oral Absorption of Efflux Transporter Substrate Drugs: Does Delayed Gastric Emptying Influence Drug Transport Kinetics?

Sharma

2021

Pharmaceutics

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The oral route of drug administration is the most convenient method of drug delivery, but it is associated with variable bioavailability. Food is one of the major factors that affect oral drug absorption by influencing drug properties (e.g., solubility and dissolution rate) and physiological factors (e.g., metabolism and transport across the gastrointestinal tract). The aim of this work was to investigate the effect of food on the high-affinity intestinal efflux transporter substrate drugs. We hypothesized that transport efficiency is higher in the fed state as compared to the fasted state because of the lower intestinal lumen drug concentration due to prolonged gastric emptying time. A systematic analysis of reported clinical food-effect (FE) studies on 311 drugs was performed and the association of the efflux transport efficiency was investigated on the FE magnitude, i.e., changes in maximal plasma concentration and area under the plasma concentration–time profile curve for both solubility and permeability-limited drugs. In total, 124 and 88 drugs showed positive and negative FE, respectively, whereas 99 showed no FE. As expected, the solubility-limited drugs showed positive FE, but interestingly, drugs with a high potential for efflux transport, were associated with negative FE. Moreover, a high-fat diet was associated with a higher magnitude of negative FE for high-affinity efflux transporter substrates as compared to a low-fat diet. To account for changes in drug absorption after food intake, the prolonged gastric emptying time should be considered in the physiologically based pharmacokinetic (PBPK) modeling of orally absorbed efflux transporter substrate drugs.

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Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Food Effect on Oral Absorption of Efflux Transporter Substrate Drugs: Does Delayed Gastric Emptying Influence Drug Transport Kinetics?

Sharma

2021

Pharmaceutics

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“…Thus, specialists in the field must rely on their knowledge to adapt formulations to suit the pharmaceutical needs of the individual [50]. There are many factors to consider during personalised formulation design, some include: patient's swallowing capacity, flavour preferences, required drug dose, required drug release kinetics, presence of disease, sex, age, motor skills, and coadministered medications [184][185][186][187][188][189][190][191][192][193][194][195][196][197][198][199]. ML has the capacity to consider all these factors and predict optimal formulation design features based on an individual's requirements [154,[200][201][202].…”

Section: Machine Learning In the Pre-printing Stagementioning

confidence: 99%

Harnessing artificial intelligence for the next generation of 3D printed medicines

Elbadawi

McCoubrey

Gavins

et al. 2021

Advanced Drug Delivery Reviews

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102

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…While some drugs are intended to target the gastrointestinal tract (GIT), the majority are employed to exert a systemic therapeutic effect. Nevertheless, the oral bioavailability of most pharmaceutical compounds depends mainly on their solubility, permeability, and stability in the GIT environment [ 49 , 50 , 51 ].…”

Section: Treating Cvd Through Various Administration Routesmentioning

confidence: 99%

Focus on the Lymphatic Route to Optimize Drug Delivery in Cardiovascular Medicine

et al. 2021

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While oral agents have been the gold standard for cardiovascular disease therapy, the new generation of treatments is switching to other administration options that offer reduced dosing frequency and more efficacy. The lymphatic network is a unidirectional and low-pressure vascular system that is responsible for the absorption of interstitial fluids, molecules, and cells from the peripheral tissue, including the skin and the intestines. Targeting the lymphatic route for drug delivery employing traditional or new technologies and drug formulations is exponentially gaining attention in the quest to avoid the hepatic first-pass effect. The present review will give an overview of the current knowledge on the involvement of the lymphatic vessels in drug delivery in the context of cardiovascular disease.

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

Cited by 179 publications

References 362 publications

Meta-Analysis of Food Effect on Oral Absorption of Efflux Transporter Substrate Drugs: Does Delayed Gastric Emptying Influence Drug Transport Kinetics?

Meta-Analysis of Food Effect on Oral Absorption of Efflux Transporter Substrate Drugs: Does Delayed Gastric Emptying Influence Drug Transport Kinetics?

Harnessing artificial intelligence for the next generation of 3D printed medicines

Focus on the Lymphatic Route to Optimize Drug Delivery in Cardiovascular Medicine

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