Passive lipoidal diffusion and carrier-mediated cell uptake are both important mechanisms of membrane permeation in drug disposition

Mol Pharm. 2014 Jun 2;11(6):1727-38. doi: 10.1021/mp400713v. Epub 2014 May 6.


Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal diffusion, depending on the compound's properties, membrane properties, and solution properties. The prevailing hypothesis of drug permeation continues to be successful for application and prediction in drug development. Proponents of the carrier-mediated only concept argue against passive lipoidal diffusion. However, the arguments are not supported by broad pharmaceutics literature. The carrier-mediated only concept lacks substantial supporting evidence and successful applications in drug development.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport / physiology*
  • Cell Membrane / metabolism*
  • Cell Membrane Permeability / physiology*
  • Diffusion
  • Drug Carriers / metabolism*
  • Humans
  • Pharmaceutical Preparations / metabolism*


  • Drug Carriers
  • Pharmaceutical Preparations