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Related Concept Videos

Pore Transport and Ion-Pair Transport01:17

Pore Transport and Ion-Pair Transport

Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited  but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
Drug Absorption Mechanism: Carrier-Mediated Membrane Transport01:19

Drug Absorption Mechanism: Carrier-Mediated Membrane Transport

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.
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
Cellular Membranes and Drug Transport01:24

Cellular Membranes and Drug Transport

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.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport01:23

Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport

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.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
Facilitated Diffusion01:16

Facilitated Diffusion

The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...

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High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies
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Published on: September 29, 2023

Drug structure-transport relationships.

Michael S Roberts1

  • 1School of Pharmacy and Medical Science and Sansom Institute for Health Research, University of South Australia, Adelaide, Australia. m.roberts@uq.edu.au

Journal of Pharmacokinetics and Pharmacodynamics
|November 26, 2010
PubMed
Summary
This summary is machine-generated.

This review highlights Malcolm Rowland's contributions to understanding drug pharmacokinetics from a physiological viewpoint. His work advanced drug excretion, disposition, and clearance concepts, impacting drug development and clinical applications.

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Physiological Pharmacology
  • Drug Discovery and Development

Background:

  • Malcolm Rowland's research significantly advanced the understanding of drug structure-pharmacokinetic relationships.
  • His work integrated physiological principles with drug disposition studies.

Purpose of the Study:

  • To summarize parallel research activities focusing on physiological pharmacokinetic principles.
  • To acknowledge Malcolm Rowland's foundational contributions to the field.

Main Methods:

  • Review of Malcolm Rowland's seminal work on drug excretion and disposition.
  • Application of physiological models, including the convection-dispersion model for hepatic clearance.
  • In situ organ studies and whole-body pharmacokinetic modeling.

Main Results:

  • Demonstrated the impact of pH on amphetamine excretion.
  • Clarified the disposition of aspirin and lidocaine using clearance concepts.
  • Developed and applied a physiological approach to hepatic clearance, incorporating blood transit time variability.

Conclusions:

  • Physiological pharmacokinetic modeling provides a robust framework for understanding drug behavior.
  • Malcolm Rowland's work laid the groundwork for applying pharmacokinetic principles to clinical situations and drug development.
  • The convection-dispersion model and related concepts are crucial for studying organ-specific drug clearance and interspecies scaling.