Search

Metoprolol is among the most frequently prescribed β-blockers for the treatment of various cardiovascular diseases. Genetic polymorphism within CYP2D6has been shown to affect the rate of metabolism of metoprolol. Whether metoprolol dose adjustments are indicated in CYP2D6poor metabolizers (PMs) has thus far not well been studied. The aim of this study was to determine the effect of the CYP2D6genotype on the metoprolol maintenance dose in a chronic Dutch patient population. Patients were included if they were treated with metoprolol and in whom CYP2D6genotype status was known. Patient and treatment characteristics were obtained retrospectively from the electronic healthcare records. Metoprolol maintenance dose was the primary endpoint and was defined as the last known dose that the patients had been treated with. Genotype data were categorized into four phenotypes, that is, PMs, intermediate metabolizers, extensive metabolizers, and ultra-rapid metabolizers (UMs). The endpoints were analyzed as PM versus non-PM. A total of 105 patients were included. The mean ± SD maintenance dose in PMs (n= 12) was significantly lower compared with non-PMs (n= 93), that is, 48 ± 20 versus 84 ± 53 mg, respectively (P= 0.019). No association of the CYP2D6genotype with the incidence of side effects was observed, although there was a trend for increased risk of drowsiness (P= 0.053). The results of this study show that the CYP2D6genotype is associated with the maintenance dose of metoprolol. Patients with the CYP2D6 PM phenotype may benefit from a lower metoprolol starting dose, followed by further dose titration to provide patient-tailored therapy and thereby increase the effectiveness of treatment.

The SLCO1B1c.521T>C polymorphism is associated with statin plasma levels and simvastatin-induced adverse drug reactions. We studied whether the c.521T>C polymorphism is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy, because these events are indicators of adverse drug reactions.

To investigate the influence of tagging single-nucleotide polymorphisms (SNPs) within candidate genes involved in the putative anti-inflammatory effects of statins on the effectiveness of statins in reducing the risk of myocardial infarction (MI).