Allyl Alcohol 및 Ethanol 혼합투여에 의한 혈중 농도 변화 및 독성과의 상관성

Kinetic Studies of Parent Compounds and Its Metabolite by Combined Treatment of Allyl Alcohol with Ethanol in vivo

Allyl alcohol is metabolized in the liver through two steps, first to reactive acrolein by alcohol dehydrogenase (ADH), subsequently to acrylic acid by aldehyde dehydrogenase (ALDH). Since ethanol could compete the same enzymes to be metabolized in the liver, we have determined the plasma concentrations of allyl alcohol and ethanol followed by combined treatment. Pretreatment of rats with 2g/kg ethanol followed by ip administration of 40mg/kg allyl alcohol increased the lethality significantly. Determination of in vivo blood concentrations revealed that ethanol pretreatment caused the apparent decrease in allyl alcohol clearance, whereas acetaldehyde level in blood increased significantly by allyl alcohol treatment, as determined by head space GC analysis. Treatment of 4-methylpyrazole, an inhibitor of ADH, delayed allyl alcohol elimination significantly and reduced its lethality. Collectively, these findings suggested that reduction of allyl alcohol clearance in the presence oj ethanol was mediated through ADH competitive inhibition.