Variability in Cytochrome P450-Mediated Metabolism of Cardiovascular Drugs: Clinical Implications and Practical Attempts to Avoid Potential Problems

Abstract

Cytochrome P450 (CYP) enzymes play an important role in the turnover of more than 50 cardiovascular drugs (CVDs). Variable CYP activities due to genetic polymorphism or drug interactions are important sources of variability in systemic exposure of many of these drugs. The therapeutic implications are in most cases an increased response (effect/side effects) in patients with genetically determined decreased/deficient metabolic activity or during concurrent use of CYP inhibitors. Special attention with regard to safety should be paid to several coumarin-type anticoagulants, antiarrhythmics, β-receptor antagonists and HMG-CoA reductase inhibitors (statins). Prevention of potential clinical problems associated with CYP variability is easily achieved using equally effective therapeutic alternatives that are not dependent on CYP metabolism. However, if ‘CYP sensitive’ CVDs are either the preferred or only therapeutic alternatives, restrictive use of inhibitors is advisable, whereas patient genotyping prior to treatment might be a helpful tool to apply rational (individual) doses for certain agents.