Metoprolol-lnduced Hepatitis: Rechallenge and Drug Oxidation Phenotyping

Excerpt

Metoprolol is a widely used beta-adrenoreceptor antagonist. To our knowledge, there is no report of hepatitis involving this drug as well as other beta-adrenoreceptor antagonists (1). Metoprolol is metabolized by three major oxidation pathways (2); two of them, O-dealkylation and alpha-hydroxylation, undergo genetically controlled polymorphisms correlated with that of debrisoquine oxidation (2-4). 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 many other drugs such as sparteine, perhexiline, and several other beta-adrenoreceptor antagonists (5). Poor metabolizers of debrisoquine and metoprolol exhibit