Literature DB >> 25458537

What would be the observable consequences if phospholipid bilayer diffusion of drugs into cells is negligible?

Douglas B Kell1.   

Abstract

For drug transport across (i.e., through) an intact biological membrane, two main routes are possible: drugs may cross (i) through the phospholipid bilayer portion of the membrane, and/or (ii) via proteinaceous pores or transporters. Perhaps surprisingly, there is in fact no direct scientific evidence that the first of these takes place at any significant rate because, in the experiments performed to date, it has neither been varied as an independent variable nor measured directly as a dependent variable. Using a standard hypothetico-deductive framework, I assess the intellectual and observable consequences of assuming that, for drugs, phospholipid bilayer diffusion is negligible - 'PBIN' - (i.e., may be neglected, relative to transporter-mediated transmembrane fluxes). Predictions and postdictions of the PBIN hypothesis are not refuted by available experimental evidence.
Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Entities:  

Keywords:  drug transporters; lipoidal bilayer diffusion; physiologically based pharmacokinetic modelling; systems pharmacology

Mesh:

Substances:

Year:  2014        PMID: 25458537     DOI: 10.1016/j.tips.2014.10.005

Source DB:  PubMed          Journal:  Trends Pharmacol Sci        ISSN: 0165-6147            Impact factor:   14.819


  20 in total

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2.  A palette of fluorophores that are differentially accumulated by wild-type and mutant strains of Escherichia coli: surrogate ligands for profiling bacterial membrane transporters.

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Review 3.  An Analysis of Mechanisms for Cellular Uptake of miRNAs to Enhance Drug Delivery and Efficacy in Cancer Chemoresistance.

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5.  Understanding the foundations of the structural similarities between marketed drugs and endogenous human metabolites.

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Journal:  Front Pharmacol       Date:  2015-05-13       Impact factor: 5.810

Review 6.  Individuality, phenotypic differentiation, dormancy and 'persistence' in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology.

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7.  MetMaxStruct: A Tversky-Similarity-Based Strategy for Analysing the (Sub)Structural Similarities of Drugs and Endogenous Metabolites.

Authors:  Steve O'Hagan; Douglas B Kell
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8.  Identification and functional characterization of a PDR transporter in Tripterygium wilfordii Hook.f. that mediates the efflux of triptolide.

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Review 9.  The metabolome 18 years on: a concept comes of age.

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Review 10.  Fitting Transporter Activities to Cellular Drug Concentrations and Fluxes: Why the Bumblebee Can Fly.

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Journal:  Trends Pharmacol Sci       Date:  2015-11-01       Impact factor: 14.819

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