Physico‐Chemical and Biological Factors that Influence a Drug's Cellular Permeability by Passive Diffusion

Conradi, Robert A.; Burton, Philip S.; Borchardt, R. T.

doi:10.1002/9783527614998.ch14

Cited by 44 publications

(20 citation statements)

References 64 publications

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“…3) (9,10). For many drugs, transport is mediated by passive transcellular diffusion through the apical cell membranes, across the cell proper and across the basolateral membrane (8). The ease of passive transcellular diffusion depends on the ability of the molecule to partition into cell membranes.…”

Section: Passive Diffusionmentioning

confidence: 99%

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Lipophilicity and Its Relationship with Passive Drug Permeation

2010

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In this review, we first summarize the structure and properties of biological membranes and the routes of passive drug transfer through physiological barriers. Lipophilicity is then introduced in terms of the intermolecular interactions it encodes. Finally, lipophilicity indices from isotropic solvent systems and from anisotropic membrane-like systems are discussed for their capacity to predict passive drug permeation across biological membranes such as the intestinal epithelium, the blood-brain barrier (BBB) or the skin. The broad evidence presented here shows that beyond the predictive power of lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.

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Section: Passive Diffusionmentioning

confidence: 99%

“…The interconnected monolayer of cells in the intestinal epithelium is the principle permeation barrier for oral absorption of drugs. Similarly, a special class of capillary endothelial cells interlinked by exceptionally tight junctions constitutes the main barrier for drug transport from blood to brain (8). …”

Section: Structure Of Cell Membranesmentioning

confidence: 99%

Lipophilicity and Its Relationship with Passive Drug Permeation

2010

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“…Therefore, studies on drug-transfer characteristics and mechanisms in such systems are of great importance to understand better the behavior of drugs in their pharmacokinetic phase, (174,175) their distribution in vivo, (176) and hence, the delivery problems that limit their efficiency. (177) The transport of exogeneous chemicals (and hence of the majority of common drugs) is a passive process, (178) for which it is commonly assumed that ionizable compounds can only cross biological membranes in their neutral form.…”

Section: Electrochemistry Of Drugs At Liquid/liquid Interfacesmentioning

confidence: 99%

Liquid/Liquid Interfaces, Electrochemistry atUpdate based on the original article by Frédéric Reymond, Hubert H. Girault,Encyclopedia of Analytical Chemistry, © 2000, John Wiley & Sons, Ltd

Peljo

Girault

2012

Encyclopedia of Analytical Chemistry

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This article outlines the electrochemical methodology at the interface between two immiscible electrolyte solutions (ITIES). The fundamental concepts of the thermodynamics in biphasic systems are presented in order to show how ions are distributed between the two adjacent phases and hence, how a Galvani potential difference is established at an ITIES. Polarizable and nonpolarizable ITIES are then characterized, and it is further evidenced that the classical electroanalytical methodology at a solid electrode can be directly transposed to the ITIES, thereby allowing reversible charge‐transfer reactions to be easily monitored and interpreted. This theoretical approach is completed by a review of the analytical methods used at ITIES, namely cyclic voltammetry (CV), hydrodynamic methods, spectroscopic techniques, and micro‐ and nanointerfaces (which are the biphasic analogs of micro‐ and nanoelectrodes). The last part deals with the practical applications that electrochemistry at ITIES has attracted during the past decades in the development of amperometric and coulometric ion sensors and detectors, detection of macromolecules, extraction of metal ions by interfacial formation of a complex, and assessment of the properties and lipophilicity of ionizable drugs.

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“…192 The results of these studies are described in several review articles. [193][194][195][196] The advances made by Ron's group in this area were made possible through longstanding and productive collaborations with his fellow KU faculty members including Ron's work on "identifying, screening for, and improving drug-like properties" since the 1980s has had an enormous impact throughout the pharmaceutical and biotechnology industry. Arguably, even bigger impact on the industry and science of drug development in the area of "instilling drug-like property into drug candidates" has been through Ron's contributions as an educator.…”

Section: Characterization Of Drug-like Propertiesmentioning

confidence: 99%