1999 年 59 巻 2 号 p. 75-83
The influence of diisopropyl adipate (DIA) on percutaneous absorption and subcutaneous tissue penetration of diclofenac (DF) from alcoholic gel ointment was investigated in guinea pig in vivo. Diclofenac sodium in isopropanol-water gel was applied on the shaved backs of guinea pigs and DF concentration in the plasma, cutaneous muscle and muscle beneath the application site was determined. Percutaneous absorption of DF was evaluated by area under plasma concentrationtime curve (AUC). AUC increased with increasing DIA amount (0, 2.5, 5.0, 7.5% w/w) supplemented in the gel. AUC at 2.5, 5.0 and 7.5% DIA was approximately 6, 21 and 36-fold greater than that of the control (0% DIA) gel, respectively. DF concentrations in cutaneous muscle linearly increased with DIA content. DF conentrations in muscle at 5.0 and 7.5% DIA were significantly greater than those of the control and 2.5% DIA. DF concentrations in cutaneous muscle and muscle after the addition of DIA were approximately 40 to 120 and 1.3 to 2.3 times greater than the corresponding plasma concentration, respectively. It is revealed that DF can directly penetrate into subcutaneous tissues following topical application, and that it is a promising compound as a percutaneous absorption enhancer for DF. By ethanol-water gel, the plasma concentration of DF showed a relatively quick decrease following maximum concentration as compared to that by isopropanol-water gel. DF concentrations in the muscle and plasma using alcoholic gel were significantly greater than those measured when using DIA-contained cream. It was suggested that solvents such as alcohol are needed to induce the enhancing activity of DIA.
