CLONING, EXPRESSION AND DIAGNOSIS OF HUMAN CYTOCHROME P450 2C19: THE PRINCIPAL DETERMINANT OF S-MEPHENYTOIN METABOLISM

摘要

The invention provides two novel members of the cytochrome P450 2C subfamily of enzymes, designated 2C18 and 2C19. DNA segments encoding these enzymes are also provided. The 2C19 polypeptide represents the principal human determinant of human S-mephenytoin 4'-hydroxylase activity. The invention also provides methods of identifying drugs metabolized by S-mephenytoin 4'-hydroxylase activity. Drugs shown to be metabolized by this activity should in general not be administered to individuals having, or belong to an ethnic group at risk of, a polymorphic deficiency in S-mephenytoin 4'-hydroxylase activity. The invention also provides methods of diagnosing individuals having a polymorphic deficiency.