We prepared a series of five esters of 6-dimethylaminohexanoic acid, and characterised the compounds by their NMR and IR spectra. Their ability to function as transdermal penetration enhancers was subsequently evaluated using excised human skin as a membrane, modified Franz diffusion cells, and theophylline as a model permeant. The penetration-enhancing efficiency of esters 1-5 was studied in the donor media of propylene glycol and isopropyl myristate, and expressed as the corresponding enhancement factors (EF). All the esters increased the penetration of theophylline through the skin. The enhancement factor for the most active substance, undecyl 6-dimethylaminohexanoate, was 118.5 (+/- 19) from propylene glycol.

• MeSH
• aminokapronáty * MeSH
• kožní absorpce účinky léků   MeSH
• kyselina 6-aminokapronová chemie   farmakologie   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• pomocné látky chemie   MeSH
• spektrofotometrie infračervená MeSH
• techniky in vitro MeSH
• theofylin farmakokinetika   MeSH
• vazodilatancia farmakokinetika   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokapronáty * MeSH
• kyselina 6-aminokapronová MeSH
• pomocné látky MeSH
• theofylin MeSH
• vazodilatancia 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.

• 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