Enhancement of drug absorption by noncharged detergents through membrane and P-glycoprotein binding

Seelig, A. and Gerebtzoff, G.. (2006) Enhancement of drug absorption by noncharged detergents through membrane and P-glycoprotein binding. Expert Opinion on Drug Metabolism & Toxicology, Vol. 2, H. 5. pp. 733-752.

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Official URL: http://edoc.unibas.ch/dok/A5258461

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Noncharged detergents are used as excipients in drug formulations. Until recently, they were considered as inert compounds, enhancing drug absorption essentially by improving drug solubility. However, many detergents insert into lipid membranes, although to different extents, and change the lateral packing density of membranes at high concentrations. Moreover, they bind to the efflux transporter P-glycoprotein (P-gp) and most likely to related transporters and metabolising enzymes with overlapping substrate specificities. If their affinity to P-gp is higher than that of the coadministered drug they act as modulators or inhibitors of P-gp and enhance drug absorption. Inhibition of P-gp and related proteins can, however, cause severe side effects. This paper first reviews the membrane binding propensity of different noncharged detergents (including poloxamers) and discusses their ability to bind to P-gp. Second, literature data on drug uptake enhancement by noncharged detergents, obtained in vivo and in vitro, are analysed at the molecular level. The present analysis provides the tools for an approximate and simple prior estimate of the membrane and P-gp binding ability of noncharged detergents based on a modular binding approach.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig A)
UniBasel Contributors:Seelig-Löffler, Anna
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Informa Healthcare
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:22
Deposited On:22 Mar 2012 13:29

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