ACETAMINOPHEN METABOLISM IN PATIENTS WITH DIFFERENT CYTOCHROME P-4502E1 GENOTYPES

Cytochrome P-450 (CYP) 2E1 is the major ethanol-oxidizing enzyme of th e nonalcohol dehydrogenase metabolic pathway in the liver. Recently, t he presence of genetic polymorphisms of this enzyme was confirmed. In this study, to clarify the influence of CYP2E1 genotype on alcohol met abolism, we analyzed acetaminophen metabolism in subjects with differe nt 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 t ype 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 eliminati on rate of acetaminophen were not different between patients with nonc irrhotic alcoholic liver disease within 1 week after abstinence and in normal subjects. In one patient with minimal change, there were no di fferences 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 patient s 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 short er, and the elimination rates were greater in patients with alcoholic liver disease within 1 week after abstinence than 4 to 6 weeks after a bstinence. These results suggest the possibility that alcohol metaboli sm in individuals with the c2 gene may be greater than those with the cl gene, and that the induction of CYP2E1 by ethanol in type B may occ ur more markedly than that in type A, although the sample number is to o small to obtain final conclusions.