Permeation enhancer dodecyl 6-(dimethylamino)hexanoate increases transdermal and topical delivery of adefovir: influence of pH, ion-pairing and skin species
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
18675907
DOI
10.1016/j.ejpb.2008.07.002
PII: S0939-6411(08)00273-7
Knihovny.cz E-zdroje
- MeSH
- adenin aplikace a dávkování analogy a deriváty chemie metabolismus MeSH
- antivirové látky aplikace a dávkování chemie metabolismus MeSH
- aplikace kožní MeSH
- chemie farmaceutická MeSH
- difuzní komory kultivační MeSH
- dimethylaminy MeSH
- dodekanol MeSH
- druhová specificita MeSH
- farmaceutická vehikula chemie MeSH
- kapronáty chemie farmakologie MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- kožní absorpce účinky léků MeSH
- kůže účinky léků metabolismus MeSH
- lidé MeSH
- methylaminy chemie farmakologie MeSH
- organofosfonáty aplikace a dávkování chemie metabolismus MeSH
- permeabilita MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adefovir MeSH Prohlížeč
- adenin MeSH
- antivirové látky MeSH
- dimethylaminy MeSH
- dodecyl 6-(dimethylamino)hexanoate MeSH Prohlížeč
- dodekanol MeSH
- farmaceutická vehikula MeSH
- kapronáty MeSH
- methylaminy MeSH
- organofosfonáty MeSH
Adefovir (9-(2-phosphonomethoxyethyl)adenine) is an acyclic nucleoside phosphonate currently used for the treatment of hepatitis B. The aim of this study was to evaluate the effect of permeation enhancer DDAK (6-dimethylaminohexanoic acid dodecyl ester) on the transdermal and topical delivery of adefovir. In porcine skin, DDAK enhanced adefovir flux 42 times with maximum at pH 5.8 suggesting ion pair formation. DDAK increased thermodynamic activity and stratum corneum/vehicle distribution coefficient of adefovir, as well as it directly decreased the skin barrier resistance. Maximal flux was observed already at 2% adefovir+1% DDAK. The results were confirmed in freshly excised human skin where DDAK enhanced adefovir flux 179 times to 8.9 microg/cm(2)/h. This rate of percutaneous absorption would allow for reaching effective plasma concentrations. After the topical application, adefovir concentrated in the stratum corneum with low penetration into the deeper skin layers from either aqueous or isopropyl myristate vehicle without the enhancer. With 1% DDAK, adefovir concentrations in the viable epidermis and dermis were 33-61 times higher. These results offer an attractive alternative to established routes of administration of adefovir and other acyclic nucleoside phosphonates.
Citace poskytuje Crossref.org
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