PURPOSE: Dodecyl-6-aminohexanoate (DDEAC) is a transdermal permeation enhancer with excellent activity, low toxicity, and no dermal irritation. We hypothesized that DDEAC reacts with air CO2 to form a two-chain ammonium carbamate--Transkarbam 12 (T12)--which is responsible for the enhancing effect. METHODS: DDEAC and T12 were synthesized, their structures were confirmed by spectral methods, and their enhancing activity was studied using the Franz diffusion cell and human skin. A high-performance liquid chromatography method was developed for determination of T12, and its biodegradability was evaluated using porcine esterase. RESULTS: Only the carbamate salt T12 was responsible for the high enhancing activity; DDEAC tested under argon to avoid reaction with CO2 was inactive. T12 enhanced transdermal permeation of drugs covering a wide range of physicochemical properties, including theophylline (enhancement ratio up to 55.6), clotrimazole (7.7), flobufen (5.0), and griseofulvin (24). The activity was pH-dependent, further confirming the importance of the carbamate structure. The metabolization of T12 followed a second-order kinetics with t(1/2) = 31 min. CONCLUSION: Our results indicate that T12 is a promising biodegradable permeation enhancer for a wide range of drugs, and the structurally novel group of carbamate enhancers warrants further investigation.

• MeSH
• aminokapronáty MeSH
• aplikace kožní MeSH
• butyráty aplikace a dávkování   metabolismus   MeSH
• difuzní komory kultivační MeSH
• esterasy analýza   MeSH
• griseofulvin aplikace a dávkování   metabolismus   MeSH
• karbamáty chemická syntéza   farmakologie   MeSH
• klotrimazol aplikace a dávkování   metabolismus   MeSH
• kožní absorpce MeSH
• kůže účinky léků   metabolismus   MeSH
• kyselina 6-aminokapronová chemická syntéza   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• permeabilita MeSH
• senioři MeSH
• theofylin aplikace a dávkování   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokapronáty MeSH
• butyráty MeSH
• dodecyl 6-aminocaproate MeSH Prohlížeč
• esterasy MeSH
• flobufen MeSH Prohlížeč
• griseofulvin MeSH
• karbamáty MeSH
• klotrimazol MeSH
• kyselina 6-aminokapronová MeSH
• theofylin MeSH
• transkarbam 12 MeSH Prohlížeč