Enhanced penetration of mitomycin C through hairless mouse and rat skin by enhancers with terpene moieties.

The effects of four new percutaneous absorption enhancers containing an azacyclo ring and terpene chain (1-geranylazacycloheptan-2-one (GAH), 1-farnesylazacycloheptan-2-one (FAH), 1-geranylazacyclopentan-2,5-dione (GAPD), and 1-farnesylazacyclopentan-2-one (FAP] and 1-dodecylazacycloheptan-2-one (Azone) on the percutaneous penetration of mitomycin C (MMC) through hairless mouse and rat skin in-vitro has been investigated. GAH, FAH, FAP and Azone enhanced MMC penetration by 20 to 60 times that of the control (ethanol). During the early part of the experiments, when the sink condition was maintained, FAH was the most effective for hairless mouse skin, whereas Azone showed the highest effect in the rat skin. The enhancing effect of GAPD was only about half that of the other enhancers, suggesting the importance of the polar group of the ring moiety in these compounds. The penetration of MMC through rat skin was also increased by pretreatment with these compounds, suggesting that the enhancers had a direct effect on the skin.