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Related Concept Videos

Bioavailability Enhancement: Drug Permeability Enhancement01:27

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After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt secretion,...
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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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Intestinal drug efflux: formulation and food effects.

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  • 1Department of Biopharmaceutics and Pharmaceutical Technology, School of Pharmacy, Johannes Gutenberg-University, Staudingerweg 5, 55099 Mainz, Germany.

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Summary

The intestine actively secretes drugs via transporters like P-glycoprotein (P-gp). Drug excipients and grapefruit juice can inhibit this intestinal secretion, impacting drug interactions.

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Drug Metabolism

Background:

  • The intestine, beyond absorption, plays a role in eliminating compounds via carrier systems.
  • Key drug efflux transporters, including P-glycoprotein (P-gp), are present in the intestine, similar to liver and kidney.
  • These transporters are crucial for understanding drug disposition and interactions.

Purpose of the Study:

  • To investigate P-glycoprotein-mediated intestinal secretion of talinolol in different rat jejunum segments.
  • To evaluate the inhibitory potential of common drug excipients on P-gp mediated secretion.
  • To explore the impact of grapefruit juice constituents on intestinal secretory transport.

Main Methods:

  • Single-pass perfusion of talinolol in rat jejunum, ileum, and colon.
  • Radioligand-binding assays to assess P-gp inhibition by excipients.
  • Transport studies using Caco-2 cell monolayers.

Main Results:

  • Carrier-mediated secretion of talinolol increased from jejunum to ileum to colon.
  • Common drug excipients demonstrated varying inhibitory effects on P-gp mediated secretion.
  • Grapefruit juice constituents were shown to interfere with intestinal secretory transport systems.

Conclusions:

  • Intestinal secretion varies along the length of the intestine, with higher P-gp activity in the ileum and colon.
  • Drug excipients and grapefruit juice can modulate intestinal drug secretion, potentially altering drug efficacy and safety.
  • This highlights a novel mechanism for drug-food interactions involving intestinal secretory transporters.