Effect of cyclic monoterpenes on percutaneous absorption in the case of a water-soluble drug (diclofenac sodium).
The promoting effect of cyclic monoterpenes on the percutaneous absorption of diclofenac sodium (DFS), a water-soluble drug, from gel ointments was investigated in rats. Of five cyclic monoterpenes examined, l-menthol was most effective. Plasma concentrations of diclofenac (DF) increased with increasing amounts of l-menthol in the gel ointment. L-menthol had no effect on the solubility and partition coefficient of DFS, suggesting that the thermodynamic nature of DFS in the formulation was not greatly affected. Plasma concentrations of DF arising from application of ointments containing varying amounts of the terpene were predicted from found pharmacokinetic parameters and the steady-state flux of DFS obtained from in vitro permeation experiments. Experimentally determined plasma concentration of DF agreed well with the predictions, indicating that steady-state flux in vitro well reflects percutaneous absorption in vivo.
Obata
Y
Y
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Takayama
K
K
Okabe
H
H
Nagai
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008610:Menthol / Q000494:pharmacology; D009824:Ointments; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply; D012869:Skin Absorption / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*; D013816:Thermodynamics
D001381:Azepines; D009824:Ointments; D013729:Terpenes; D004008:Diclofenac; D008610:Menthol; C035229:laurocapram