Percutaneous absorption enhancing effect and skin irritation of monocyclic monoterpenes.
The percutaneous absorption promoting effect and skin irritancy of cyclic monoterpenes were investigated in rats and with rabbits, respectively. Ketoprofen (KPF) was applied to rat skin in gel ointments containing various cyclic monoterpenes. Plasma concentrations of KPF markedly increased with the addition of the hydrocarbons of cyclic monoterpenes such as trans-p-menthane and d-limonene, whereas no significant enhancing effect was observed in the cases of other terpenes such as l-menthol, l-menthone and 1,8-cineole. The lipophilicity of the enhancers seems the important factor in promoting penetration of KPF through the skin. The enhancing activity of d-limonene was found to be much higher than that of Azone. Irritancy of the hydrocarbons of cyclic monoterpenes and Azone to the skin was evaluated using a Draize scoring method with rabbits. No change was observed on the skin surface when ethanol containing 2% of the hydrocarbons was applied to the dorsal skin, though a slight edema and erythema were observed in the case of Azone. In particular, an obvious difference was observed in the erythema formation between Azone and the hydrocarbons of cyclic monoterpenes.
Okabe
H
H
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Obata
Y
Y
Takayama
K
K
Nagai
T
T
D000818:Animals; D001381:Azepines / Q000009:adverse effects / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D053138:Cyclohexenes; D005079:Excipients / Q000009:adverse effects; D005782:Gels; D007509:Irritants; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077222:Limonene; D008297:Male; D009824:Ointments; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D012995:Solubility; D013729:Terpenes / Q000009:adverse effects / Q000494:pharmacology*
D001381:Azepines; D053138:Cyclohexenes; D005079:Excipients; D005782:Gels; D007509:Irritants; D009824:Ointments; D013729:Terpenes; C035229:laurocapram; D007660:Ketoprofen; D000077222:Limonene