Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes.
Cytochrome P-450 (CYP) 2E1 is the major ethanol-oxidizing enzyme of the nonalcohol dehydrogenase metabolic pathway in the liver. Recently, the presence of genetic polymorphisms of this enzyme was confirmed. In this study, to clarify the influence of CYP2E1 genotype on alcohol metabolism, we analyzed acetaminophen metabolism in subjects with different CYP2E1 genotypes. In normal subjects, a half-life of acetaminophen from blood was the longest in type A (c1/c1) and was the shortest in type C (c2/c2). The elimination rate in type C was more than twice that of type A and type B (c1/c2). In type A, both half-life and elimination rate of acetaminophen were not different between patients with noncirrhotic alcoholic liver disease within 1 week after abstinence and in normal subjects. In one patient with minimal change, there were no differences in both half-life and elimination rate within 1 and 6 weeks after abstinence. On the other hand, in type B, half-life was shorter and the elimination rate was greater in alcoholic noncirrhotic patients within 1 week after abstinence than in alcoholic patients with type A and in normal subjects with type B. In type B, half-lives were shorter, and the elimination rates were greater in patients with alcoholic liver disease within 1 week after abstinence than 4 to 6 weeks after abstinence. These results suggest the possibility that alcohol metabolism in individuals with the c2 gene may be greater than those with the c1 gene, and that the induction of CYP2E1 by ethanol in type B may occur more markedly than that in type A, although the sample number is too small to obtain final conclusions.
Ueshima
Y
Y
Department of Internal Medicine, Kanazawa Medical University, Shikawa, Japan.
Tsutsumi
M
M
Takase
S
S
Matsuda
Y
Y
Kawahara
H
H
D000082:Acetaminophen / Q000493:pharmacokinetics*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000431:Ethanol / Q000493:pharmacokinetics; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000201:enzymology; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000235:genetics / Q000534:rehabilitation; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000235:genetics / Q000534:rehabilitation; D008111:Liver Function Tests; D008657:Metabolic Clearance Rate / Q000235:genetics; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012016:Reference Values; D013695:Temperance
D000082:Acetaminophen; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating