Abstract
The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication.This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness).The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.
Highlights
This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions
Particular focus is directed towards non-disease dependent conditions, GI diseases, as well as systemic diseases that change the GI tract conditions
The GI tract physiology in healthy adult subjects and its impact on oral drug absorption has been extensively studied in the past decades and comprehensive reviews can be found in the literature (Bergstrom et al, 2014; Dressman and Reppas, 2010)
Summary
The GI tract physiology in healthy adult subjects and its impact on oral drug absorption has been extensively studied in the past decades and comprehensive reviews can be found in the literature (Bergstrom et al, 2014; Dressman and Reppas, 2010). The concentration of bile salts ranges from 2.5 to 5.9 mM in the duodenum and from 1.4 mM to 5.5 mM in the jejunum. Few studies have determined the regional bile salt level in the fed state, and reported values between 3.6 and 24.0 mM in the duodenum and 4.5 and 8.0 mM in the jejunum. The rank order of relative bile salt concentration in the duodenum was reported as follows: taurocholic acid> glycocholate> glycochenodeoxycholate> glycodeoxycholate> taurochenodeoxycholate> taurodeoxycholate. The relative composition of bile salts is similar between fasted and fed state in the upper GI tract as well as in the lower bowel (Diakidou et al, 2009; Perez de la Cruz Moreno et al, 2006; Riethorst et al, 2016). A large database on the human microbiome, including a variety of species for healthy and diseased humans can be found in the Human Microbiome Project Consortium report (Human Microbiome Project, 2012)
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