Τίτλος:
Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2021 The Authors
Συγγραφείς:
Vinarov, Z.
Abdallah, M.
Agundez, J.A.G.
Allegaert, K.
Basit, A.W.
Braeckmans, M.
Ceulemans, J.
Corsetti, M.
Griffin, B.T.
Grimm, M.
Keszthelyi, D.
Koziolek, M.
Madla, C.M.
Matthys, C.
McCoubrey, L.E.
Mitra, A.
Reppas, C.
Stappaerts, J.
Steenackers, N.
Trevaskis, N.L.
Vanuytsel, T.
Vertzoni, M.
Weitschies, W.
Wilson, C.
Augustijns, P.
Περιοδικό:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Λέξεις-κλειδιά:
bile salt; buffer; drug; enzyme; phospholipid; polymer; proton pump inhibitor; drug, age; anorexia; Article; ascending colon; bariatric surgery; blood; cachexia; cell membrane permeability; chemical composition; chronic constipation; chronic disease; colloid; dose calculation; drug absorption; drug activation; drug degradation; drug formulation; drug inactivation; drug solubility; drug toxicity; enterohepatic circulation; epithelium cell; fasting; fat intake; feeding; gastrointestinal tract; gastrointestinal transit; geriatrics; human; ileum; intestinal dysmotility; intestine flora; intestine fluid; intestine resection; intestine transit time; lymph; nonhuman; osmolality; particle size; pediatrics; pharmacokinetic parameters; priority journal; sex difference; small intestine content; solid state; stomach emptying; stomach pH; stomach volume; ultrastructure; viscosity; aged; child; female; food drug interaction; gastrointestinal tract; intestine absorption; male; metabolism; oral drug administration; pharmacokinetics, Administration, Oral; Aged; Child; Female; Food-Drug Interactions; Gastrointestinal Tract; Humans; Intestinal Absorption; Male; Pharmaceutical Preparations; Pharmacokinetics
DOI:
10.1016/j.ejps.2021.105812
