The objective of this work was to investigate feasibility of transdermal and dermal delivery of adefovir (9-(2-phosphonomethoxyethyl)adenine), a broad-spectrum antiviral from the class of acyclic nucleoside phosphonates. Transport of 2% adefovir through and into porcine skin and effects of various solvents, pH, and permeation enhancers were studied in vitro using Franz diffusion cell. From aqueous donor samples, adefovir flux through the skin was 0.2-5.4 microg/cm2/h with greatest permeation rate at pH 7.8. The corresponding adefovir skin concentrations reached values of 120-350 microg/g of tissue. Increased solvent lipophilicity resulted in higher skin concentration but had only minor effect on adefovir flux. A significant influence of counter ions on both transdermal and dermal transport of adefovir zwitterion was observed at pH 3.4. Permeation enhancer dodecanol was ineffective, 1-dodecylazepan-2-one (Azone) and dodecyl 2-(dimethylamino)propionate (DDAIP) showed moderate activity. The highest adefovir flux (11.3+/-3.6 microg/cm2/h) and skin concentration (1549+/-416 microg/g) were achieved with 1% Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium 5-(dodecyloxycarbonyl)pentylcarbamate) at pH 4. This study suggests that, despite its hydrophilic and ionizable nature, adefovir can be successfully delivered through the skin.

• MeSH
• adenin analogy a deriváty   aplikace a dávkování   farmakokinetika   MeSH
• antivirové látky aplikace a dávkování   farmakokinetika   MeSH
• aplikace kožní MeSH
• financování organizované MeSH
• koncentrace vodíkových iontů MeSH
• kožní absorpce účinky léků   MeSH
• lidé MeSH
• organofosfonáty aplikace a dávkování   farmakokinetika   MeSH
• permeabilita MeSH
• pomocné látky MeSH
• rozpouštědla MeSH
• systémy cílené aplikace léků MeSH
• techniky in vitro MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé 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 analogy a deriváty   aplikace a dávkování   chemie   metabolismus   MeSH
• antivirové látky chemie   metabolismus   MeSH
• aplikace kožní MeSH
• chemie farmaceutická MeSH
• difuzní komory kultivační MeSH
• druhová specificita MeSH
• farmaceutická vehikula chemie   MeSH
• kapronáty farmakologie   chemie   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• kožní absorpce účinky léků   MeSH
• kůže metabolismus   účinky léků   MeSH
• lidé MeSH
• methylaminy farmakologie   chemie   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
• práce podpořená grantem MeSH