• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.407-412
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• 2001

Many drugs are primarily metabolized by the cytochrome P450s (CYPs). Drug metabolites would be important allergens for adverse drug reactions such as drug eruptions. Skin tests with a suspected drug have conducted to identify causative drugs of drug eruptions, with vehicles such as white petrolatum, DMSO, ethanol. This study will compare the expression of rat CYP isozyme mRNAs between the skin and the liver, with examining an effect of the vehicles on the cutaneous CYPs using semi-quantitative RT-PCR. Thirty-two Sprague-Dawley rats between the ages of six and eight weeks were divided as four groups. One group was used to compare the constitutive mRNA expression between skin and liver, while the others were to examine the effects of three vehicles. The ratios of expression of CYP1A2, CYP2B1/2, CYP2E1, CYP3A1, and CYP4A1 were significantly higher in the liver than the skin. However, CYP1A1 and CYP2C11 were higher in the skin than liver. The effects of vehicles were quite different; white petrolatum significantly induced CYP1A1 (p=0.012) and CYP2C11 mRNAs, while ethanol inhibited CY P1A1 and CYP2B1/2. DMSO did not make any changes. The results suggest that rat skin can participate in drug metabolism with their own CYP isozymes. The effects of vehicles on the cutaneous CYP expression should not be ignored and may be applied for determination of an appropriate vehicle for certain drug(s).

• Archives of Pharmacal Research
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• v.11 no.3
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• pp.185-196
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• 1988

The inflence of hydrophilic vehicles on percutaneous absorption rate of griseofulvin was studied using intact skin of full thickness of hairless rat. The in vitro absorption rates were used as the characteristics for deciding the optimum formula of ointment vehicles. The optimum formula of vehicle compositions for maximum absorption rate was obtained from the polynomial regression equation and the two graphical techniques, contour graph and partial derivative graph. It was composed of sodium lauryl sulfate (1.65 W /W%), white petrolatum (16.5 W /W%), propylene glycol (12.0 W /W%), and stearyl alcohol (19.6W /W%). The experimental value obtained from the optimum formula and the prediction value were 33.99 and 33.87 ${\mu}g/\sqrt{min}$, respectively. From these results, it was believed that optimum formula for semisolid dosage forms could be obtained from the application of the optimization technique used in this study.