Abstract 18356: The Breast Cancer Resistance Protein (BCRP) c.421C>A Single Nucleotide Polymorphism Increases Steady-state Plasma Concentration of Rosuvastatin
Background: The hepatic efflux transporter BCRP (ABCG2) c.421C>A (p.Gln141Lys) single nucleotide polymorphism (SNP) has previously been shown to increase the cholesterol-lowering efficacy of rosuvastatin.
Hypotheses: We hypothesised that the previously demonstrated increase in rosuvastatin plasma concentration following single-dose pharmacokinetic studies would be replicated in steady-state plasma concentration following 3 months rosuvastatin therapy, and that such concentrations would correlate inversely with low-density lipoprotein cholesterol (LDL-C) levels.
Methods: Acute coronary syndrome (ACS) patients (n = 191) received 10 mg rosuvastatin daily for 3 months, as part of a clinical trial (SPACE ROCKET). Both rosuvastatin plasma concentration and LDL-C were measured after 3 months treatment. Patients were genotyped for the BCRP c.421C>A SNP. Differences in rosuvastatin plasma concentration and LDL-C between genotype groups were assessed using Kruskal-Wallis ANOVA and one-way between-groups ANOVA with a test for linearity, respectively. The relationship between plasma concentration and LDL-C level was assessed using Spearman's rank order correlation.
Results: Following 3 months treatment with 10 mg rosuvastatin, we observed significant differences in both rosuvastatin plasma concentration and LDL-C between BCRP genotypes groups (see Table). We observed a significant inverse correlation between rosuvastatin plasma concentration and 3-month LDL-C level (Spearman's rho = −0.255, p < 0.0005).
Conclusion: In addition to increased efficacy, the BCRP c.421C>A SNP predicts increased rosuvastatin steady-state plasma concentration amongst ACS patients. This observation supports previous suggestions that decreased enteric and hepatic efflux of rosuvastatin may explain the increased rosuvastatin cholesterol-lowering efficacy observed with this SNP.
- © 2010 by American Heart Association, Inc.