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Related Concept Videos

Factors Influencing Drug Absorption: Disease States and Pharmacology01:25

Factors Influencing Drug Absorption: Disease States and Pharmacology

Multiple disease states can significantly influence the oral drug absorption process by affecting blood flow and the functionality of the gastrointestinal (GI) system. Various GI diseases, including conditions that alter GI motility, such as diarrhea, decreased acid secretions (achlorhydria), and infections, have been associated with reduced drug absorption.
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
Drug Absorption: Factors Affecting GI Absorption01:19

Drug Absorption: Factors Affecting GI Absorption

The process of oral drug absorption can be influenced by several factors. Weakly acidic drugs tend to be absorbed more readily from the stomach due to their nonionized state. However, absorption may be less efficient in the upper intestine, where drugs are often ionized. Interestingly, despite the stomach's apparent advantage for drug absorption, its mucous layer can hinder diffusion. Its surface area is also smaller than the intestine's, which can further slow down the absorption rate.
In...
Factors Influencing Drug Absorption: Physicochemical Parameters01:22

Factors Influencing Drug Absorption: Physicochemical Parameters

The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
Factors Influencing Drug Absorption: Anatomical Parameters01:23

Factors Influencing Drug Absorption: Anatomical Parameters

Drug absorption involves the movement of drugs from the point of administration into the systemic circulation. Initially, Gastrointestinal (GI) motility propels the drug through the digestive tract and into the stomach. However, the stomach's high acidity and limited surface area restrict its role in drug absorption for most drugs. The drug then moves from the stomach to the small intestine via gastric emptying, which can be slowed by various factors, including interactions with other...
Bioavailability: Influencing Factors01:22

Bioavailability: Influencing Factors

Bioavailability refers to the extent and rate at which a drug reaches systemic circulation in its active form. Extent refers to the amount of the drug that makes it into circulation, while rate is the speed at which it enters circulation. It is influenced by several factors critical for optimizing drug formulations, dosing regimens, and therapeutic outcomes.Physicochemical properties of drugs and formulationsThe solubility, stability, and dissolution rate of a drug significantly impact its...

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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

Acetaminophen changes intestinal epithelial cell membrane properties, subsequently affecting absorption processes.

Christine Schäfer1, Klaus Rudolf Schröder, Otmar Höglinger

  • 1BioMed-zet Life Science GmbH, Linz, Austria.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|August 31, 2013
PubMed
Summary
This summary is machine-generated.

Acetaminophen (APAP) alters intestinal cell membrane properties, reducing substance absorption. This impacts drug bioavailability and requires consideration for therapeutic optimization.

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Area of Science:

  • Gastroenterology
  • Pharmacology
  • Cell Biology

Background:

  • Acetaminophen (APAP) effects on intestinal barrier function are not well understood.
  • APAP may alter the bioavailability of co-administered drugs or dietary components.
  • Investigating APAP's impact on enterocytic membrane properties is crucial for predicting absorption.

Purpose of the Study:

  • To investigate how acetaminophen (APAP) influences enterocytic cell membrane properties.
  • To determine the effect of APAP on intestinal barrier function and substance absorption.
  • To elucidate the mechanisms by which APAP affects Caco-2 cell membrane characteristics.

Main Methods:

  • Cytotoxicity assessed via LDH assay.
  • Transepithelial electrical resistance (TER) and cell capacitance measured using impedance monitoring.
  • Membrane permeability evaluated using FITC-dextrans.
  • Efflux transporter activity (MDR1) assessed with Rh123.
  • Scanning electron microscopy (SEM) used for membrane topography and microvilli analysis.
  • Western blotting employed to determine expression of intestinal alkaline phosphatase (Alpi) and tight junction protein 1 (TJP1).

Main Results:

  • APAP altered the apical cell surface, decreasing microvilli count and Alpi expression.
  • APAP reduced TJP1 expression, indicating effects on tight junctions.
  • Membrane integrity increased, while cell capacitance decreased over time.
  • Permeability to small molecules was reduced by APAP.
  • APAP enhanced the activity of the MDR1 efflux transporter.

Conclusions:

  • Acetaminophen (APAP) modifies Caco-2 cell membrane properties through multiple mechanisms.
  • APAP reduces the intestinal permeability of administered substances.
  • These findings have implications for optimizing drug therapy and understanding drug-drug interactions.