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Cellular Membranes and Drug Transport01:24

Cellular Membranes and Drug Transport

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Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
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Hepatic Drug Clearance: Role of Transporters01:14

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In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
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Drug Absorption Mechanism: Passive Membrane Transport01:23

Drug Absorption Mechanism: Passive Membrane Transport

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Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either...
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Facilitated Transport01:19

Facilitated Transport

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The chemical and physical properties of plasma membranes cause them to be selectively permeable. Since plasma membranes have both hydrophobic and hydrophilic regions, substances need to be able to transverse both regions. The hydrophobic area of membranes repels substances such as charged ions. Therefore, such substances need special membrane proteins to cross a membrane successfully. In  facilitated transport, also known as facilitated diffusion, molecules and ions travel across a...
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Drug Absorption Mechanism: Carrier-Mediated Membrane Transport01:19

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Certain large, lipid-insoluble drug molecules that resemble amino acids, peptides, or glucose, require specialized carrier proteins to facilitate their diffusion across cell membranes. This transport can occur through either facilitated diffusion, which does not require energy input, or active transport, which does require energy input.
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Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport01:23

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Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
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Expanding the Toolkit for In Vivo Imaging of Axonal Transport
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Imaging techniques to study drug transporter function in vivo.

Nicolas Tournier1, Bruno Stieger2, Oliver Langer3

  • 1Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France.

Pharmacology & Therapeutics
|April 24, 2018
PubMed
Summary
This summary is machine-generated.

Molecular imaging offers a non-invasive way to study drug transporters in humans, advancing pharmacokinetic research. This technology aids drug development and medicine by revealing transporter functions and influences.

Keywords:
Magnetic resonance imagingMembrane transportersMolecular imagingPharmacokineticsPositron emission tomographySingle photon emission computed tomography

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Area of Science:

  • Pharmacology
  • Biophysics
  • Medical Imaging

Background:

  • Membrane transporters significantly influence drug pharmacokinetics and tissue exposure.
  • Traditional methods for studying transporters in vivo are invasive and not suitable for human application.
  • Advancements in imaging technologies, probes, and data analysis have enabled non-invasive assessments.

Purpose of the Study:

  • To provide an overview of the current state of molecular imaging for drug transporters.
  • To focus on human studies evaluating transport systems for imaging agents and drug pharmacokinetics.
  • To highlight the potential of imaging in drug development and clinical medicine.

Main Methods:

  • Review of recent advancements in molecular imaging instrumentation and probe development.
  • Analysis of data from human studies investigating drug transporter function.
  • Inclusion of relevant animal studies to supplement human data where necessary.

Main Results:

  • Molecular imaging allows for non-invasive or minimally invasive determination of pharmacokinetic parameters in various tissues and organs.
  • Imaging can characterize transport systems for imaging agents and determine drug pharmacokinetics in humans.
  • Studies demonstrate the potential to elucidate mechanistic aspects of transporter function.

Conclusions:

  • Molecular imaging holds significant promise for studying drug transporters in humans, despite existing methodological limitations.
  • Imaging is poised to become a crucial tool in both drug development and clinical practice.
  • Imaging can reveal the impact of genetics, disease states, and drug-drug interactions on transporter activity.