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

期刊

TRENDS IN PHARMACOLOGICAL SCIENCES
卷 36, 期 1, 页码 15-21

出版社

CELL PRESS
DOI: 10.1016/j.tips.2014.10.005

关键词

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

资金

  1. Biotechnology and Biological Sciences Research Council [BB/M017702/1]
  2. BBSRC [BB/M017702/1] Funding Source: UKRI
  3. Biotechnology and Biological Sciences Research Council [BB/M017702/1] Funding Source: researchfish

向作者/读者索取更多资源

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.

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