Intestinal drug absorption and bioavailability: beyond involvement of single transport function

2003 ◽  
Vol 55 (4) ◽  
pp. 429-433 ◽  
Author(s):  
Hans Lennernäs
Keyword(s):  
Drug Absorption ◽  
Transport Function ◽  
Intestinal Drug Absorption

scholarly journals Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 272
Author(s):  
Arik Dahan ◽  
Isabel González-Álvarez
Keyword(s):  
Drug Absorption ◽  
Unmet Needs ◽  
Drug Formulation ◽  
Fluid Composition ◽  
Mucosal Cell ◽  
Special Issue ◽  
Junction Resistance ◽  
Intestinal Drug Absorption ◽  
Carrier Mediated Transport ◽  
Mechanistic Basis

The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g., the surrounding pH, fluid composition, transporters expression, metabolic enzymes activity, tight junction resistance, different morphology along the GIT, variable intestinal mucosal cell differentiation, changes in drug concentration (in cases of carrier-mediated transport), thickness and types of mucus, and resident microflora. Each of these variables, alone or in combination with others, can fundamentally alter the solubility/dissolution, the intestinal permeability, and the overall absorption of various drugs. This is the underlying mechanistic basis of regional-dependent intestinal drug absorption, which has led to many attempts to deliver drugs to specific regions throughout the GIT, aiming to optimize drug absorption, bioavailability, pharmacokinetics, and/or pharmacodynamics. In this Editorial we provide an overview of the Special Issue "Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation". The objective of this Special Issue is to highlight the current progress and to provide an overview of the latest developments in the field of regional-dependent intestinal drug absorption and delivery, as well as pointing out the unmet needs of the field.

scholarly journals Robotic screening of intestinal drug absorption

2020 ◽  
Vol 4 (5) ◽  
pp. 485-486
Author(s):  
Abdul W. Basit ◽  
Christine M. Madla ◽  
Francesca K. H. Gavins
Keyword(s):  
Drug Absorption ◽  
Intestinal Drug Absorption

ChemInform Abstract: In vitro Systems for Studying Intestinal Drug Absorption

ChemInform ◽  
2010 ◽  
Vol 26 (31) ◽  
pp. no-no
Author(s):  
K. M. HILLGREN ◽  
A. KATO ◽  
R. T. BORCHARDT
Keyword(s):  
Drug Absorption ◽  
Intestinal Drug Absorption ◽  
In Vitro Systems

Expression, regulation and function of intestinal drug transporters: an update

2017 ◽  
Vol 398 (2) ◽  
pp. 175-192 ◽  
Author(s):  
Janett Müller ◽  
Markus Keiser ◽  
Marek Drozdzik ◽  
Stefan Oswald
Keyword(s):  
Drug Absorption ◽  
Drug Transport ◽  
Drug Exposure ◽  
Oral Absorption ◽  
Basolateral Membrane ◽  
Oral Drug ◽  
Human Intestine ◽  
Intestinal Drug Absorption ◽  
Intestinal Transporters ◽  
And Function

Abstract Although oral drug administration is currently the favorable route of administration, intestinal drug absorption is challenged by several highly variable and poorly predictable processes such as gastrointestinal motility, intestinal drug solubility and intestinal metabolism. One further determinant identified and characterized during the last two decades is the intestinal drug transport that is mediated by several transmembrane proteins such as P-gp, BCRP, PEPT1 and OATP2B1. It is well-established that intestinal transporters can affect oral absorption of many drugs in a significant manner either by facilitating their cellular uptake or by pumping them back to gut lumen, which limits their oral bioavailability. Their functional relevance becomes even more apparent in cases of unwanted drug-drug interactions when concomitantly given drugs that cause transporter induction or inhibition, which in turn leads to increased or decreased drug exposure. The longitudinal expression of several intestinal transporters is not homogeneous along the human intestine, which may have functional implications on the preferable site of intestinal drug absorption. Besides the knowledge about the expression of pharmacologically relevant transporters in human intestinal tissue, their exact localization on the apical or basolateral membrane of enterocytes is also of interest but in several cases debatable. Finally, there is obviously a coordinative interplay of intestinal transporters (apical–basolateral), intestinal enzymes and transporters as well as intestinal and hepatic transporters. This review aims to give an updated overview about the expression, localization, regulation and function of clinically relevant transporter proteins in the human intestine.

Drug Absorption II: Effect of Fasting on Intestinal Drug Absorption

1969 ◽  
Vol 58 (10) ◽  
pp. 1200-1202 ◽  
Author(s):  
J.T. Doluisio ◽  
G.H. Tan ◽  
N.F. Billups ◽  
L. Diamond
Keyword(s):  
Drug Absorption ◽  
Intestinal Drug Absorption

scholarly journals Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives

2020 ◽  
Vol 117 (27) ◽  
pp. 16009-16018 ◽  
Author(s):  
Ling Zou ◽  
Peter Spanogiannopoulos ◽  
Lindsey M. Pieper ◽  
Huan-Chieh Chien ◽  
Wenlong Cai ◽  
...  
Keyword(s):  
Drug Absorption ◽  
Azo Dye ◽  
Pharmacokinetic Studies ◽  
Unintended Effects ◽  
Drug Products ◽  
Intestinal Drug Absorption ◽  
High Concentrations ◽  
Gut Microbial Community ◽  
Selection Of

Food and drug products contain diverse and abundant small-molecule additives (excipients) with unclear impacts on human physiology, drug safety, and response. Here, we evaluate their potential impact on intestinal drug absorption. By screening 136 unique compounds for inhibition of the key intestinal transporter OATP2B1 we identified and validated 24 potent OATP2B1 inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or noninhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R−N=N−R′) dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient and a potent inhibitor of OATP2B1, decreased the plasma level of the OATP2B1 substrate fexofenadine, suggesting that FD&C Red No. 40 has the potential to block drug absorption through OATP2B1 inhibition in vivo. However, the gut microbiomes of multiple unrelated healthy individuals as well as diverse human gut bacterial isolates were capable of inactivating the identified azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine and provide a framework for the data-driven selection of excipients. Furthermore, the ubiquity and genetic diversity of gut bacterial azoreductases coupled to experiments in conventionally raised and gnotobiotic mice suggest that variations in gut microbial community structure may be less important to consider relative to the high concentrations of azo dyes in food products, which have the potential to saturate gut bacterial enzymatic activity.

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