Permeation enhancer dodecyl 6-(dimethylamino)hexanoate increases transdermal and topical delivery of adefovir: influence of pH, ion-pairing and skin species
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18675907
DOI
10.1016/j.ejpb.2008.07.002
PII: S0939-6411(08)00273-7
Knihovny.cz E-resources
- MeSH
- Adenine administration & dosage analogs & derivatives chemistry metabolism MeSH
- Antiviral Agents administration & dosage chemistry metabolism MeSH
- Administration, Cutaneous MeSH
- Chemistry, Pharmaceutical MeSH
- Diffusion Chambers, Culture MeSH
- Dimethylamines MeSH
- Dodecanol MeSH
- Species Specificity MeSH
- Pharmaceutical Vehicles chemistry MeSH
- Caproates chemistry pharmacology MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Skin Absorption drug effects MeSH
- Skin drug effects metabolism MeSH
- Humans MeSH
- Methylamines chemistry pharmacology MeSH
- Organophosphonates administration & dosage chemistry metabolism MeSH
- Permeability MeSH
- Swine MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- adefovir MeSH Browser
- Adenine MeSH
- Antiviral Agents MeSH
- Dimethylamines MeSH
- dodecyl 6-(dimethylamino)hexanoate MeSH Browser
- Dodecanol MeSH
- Pharmaceutical Vehicles MeSH
- Caproates MeSH
- Methylamines MeSH
- Organophosphonates 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.
References provided by Crossref.org
Esters of terpene alcohols as highly potent, reversible, and low toxic skin penetration enhancers
