TY - JOUR
T1 - Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review
AU - Vinarov, Z.
AU - Abdallah, M.
AU - Agundez, J.A.G.
AU - Allegaert, K.
AU - Basit, A.W.
AU - Braeckmans, M.
AU - Ceulemans, J.
AU - Corsetti, M.
AU - Griffin, B.T.
AU - Grimm, M.
AU - Keszthelyi, D.
AU - Koziolek, M.
AU - Madla, C.M.
AU - Matthys, C.
AU - McCoubrey, L.E.
AU - Mitra, A.
AU - Reppas, C.
AU - Stappaerts, J.
AU - Steenackers, N.
AU - Trevaskis, N.L.
AU - Vanuytsel, T.
AU - Vertzoni, M.
AU - Weitschies, W.
AU - Wilson, C.
AU - Augustijns, P.
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.
KW - Variation
KW - Fasted and fed state
KW - Physiology
KW - Pediatrics and geriatrics
KW - Diseases
KW - Drug formulation
KW - PROTON PUMP INHIBITORS
KW - HUMAN INTESTINAL FLUID
KW - COLONIC BACTERIAL METABOLISM
KW - TYROSINE KINASE INHIBITORS
KW - OROCECAL TRANSIT-TIME
KW - SHORT-BOWEL SYNDROME
KW - IN-VITRO
KW - ENTEROHEPATIC RECIRCULATION
KW - LYMPHATIC TRANSPORT
KW - DOSAGE FORMS
U2 - 10.1016/j.ejps.2021.105812
DO - 10.1016/j.ejps.2021.105812
M3 - (Systematic) Review article
C2 - 33753215
SN - 0928-0987
VL - 162
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
M1 - 105812
ER -