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Metoprolol‐induced hepatitis: Is the rate of oxidation related to drug‐induced hepatotoxicity?
Author(s) -
Lennard M. S.
Publication year - 1989
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840090126
Subject(s) - metoprolol , debrisoquine , pharmacology , cyp2d6 , drug , pharmacokinetics , drug interaction , medicine , chemistry , cytochrome p450 , metabolism
Metoprolol is as widely used beta‐adrenoreceptor antagonist. There is no report of hepatitis involving this drug as well as other beta‐adrenoreceptor antagonists. Metoprolol is metabolized by three major oxidation pathways. Two of them, Odealkylation and alpha‐hydroxylation, undergo genetically controlled polymorphisms correlated with that of debrisoquine oxidation. This finding strongly suggests that metoprolol oxidation depends at least partly on the same isozyme of cytochrome P‐450 involved in the genetic polymorphism of oxidation of debrisoquine and other drugs such as sparteine, perhexiline, and other beta‐adrenoreceptor antagonists. Poor metabolizers of debrisoquine and metoprolol exhibit abnormal pharmacokinetics of metoprolol, which can result in an overdose after administration of a standard dose. There is a clear association between impairment of debrisoquine oxidation and susceptibility to develop liver injury with perhexiline. Does such an association exist for metoprolol? We report the first case of hepatitis induced by metoprolol and the result of drug oxidation phenotyping.