The effect of ethanol on the simultaneous transport and metabolism of methyl p-hydroxybenzoate in excised skin of Yucatan micropig.
The effects of ethanol on the simultaneous transport and metabolism of methyl p-hydroxybenzoate (HBM) were investigated in the skin of Yucatan micropig in vitro. It was found that transesterification occurred in the permeation studies involving ethanol. This was confirmed by monitoring the flux of ethyl p-hydroxybenzoate (HBE) into the receptor phase, as well as by monitoring the fluxes of HBM and p-hydroxybenzoic acid (HBA). The apparent flux of total HBM was decreased. The solubility of HBM increased with ethanol concentration, thus, the activity of HBM in ethanol solution became low because we used 10 mM HBM solution for permeation studies. The enhancement factor (E) was calculated to correct the activity. E increased with increasing the flux of ethanol, thus, ethanol may function as an enhancer of HBM transport. The hydrolysis of HBM to HBA was inhibited, whereas transesterification of HBM to HBE was induced at all concentrations of ethanol used (10-40%). The formation of HBE occurred much more readily than that of HBA at all concentrations of ethanol used.
Oh
S Y
SY
Showa Pharmaceutical University, 3-3165 Higashi-Tamagawa-Gakuen, Machida, 194-8543, Tokyo, Japan.
Fujii
M
M
Takeda
Y
Y
Yoda
K
K
Utoguchi
N
N
Matsumoto
M
M
Watanabe
Y
Y
D000818:Animals; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics*; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D010226:Parabens / Q000378:metabolism / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature
D002492:Central Nervous System Depressants; D010226:Parabens; D014677:Pharmaceutical Vehicles; C012313:ethyl-p-hydroxybenzoate; D000431:Ethanol; C015358:methylparaben