An update on efflux and uptake transporters as determinants of statin response.
Statins are used in the treatment of dyslipidemia promoting primary and secondary prevention against detrimental cardiovascular events. ATP-binding cassette (ABC) and solute carrier (SLC) membrane transporters transport statins across the cell membrane. Differences in drug transporter tissue expression and activity contribute to variability in statin pharmacokinetics (PK) and response. Areas covered: The purpose of this review is to discuss factors impacting transporter expression and the effect this has on statin efficacy and safety. Previous studies have demonstrated that genetic polymorphisms, drug-drug interactions (DDI), nuclear receptors, and microRNAs affect statin PK and pharmacodynamics. Expert opinion: Genetic variants of ABCG2 and SLCO1B1 transporters affect statin PK and, as a result, the intended lipid-lowering response. However, the effect size is small, limiting its applicability in clinical practice. Furthermore, genetic variants do not totally explain the observed intervariability in statin response. Thus, it is likely that transcriptional and post-transcriptional regulation of drug transporters are also highly involved. Further studies are required to understand the contribution of each of these new factors in statin disposition and toxicity.
['Rocha|Karina Cunha E|KCE|', 'Pereira|Beatriz Maria Veloso|BMV|', 'Rodrigues|Alice Cristina|AC|']
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 D000818:Animals D001692:Biological Transport D002318:Cardiovascular Diseases D004347:Drug Interactions D050171:Dyslipidemias D014644:Genetic Variation D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D027381:Liver-Specific Organic Anion Transporter 1 D009363:Neoplasm Proteins D011110:Polymorphism, Genetic D016896:Treatment Outcome
ABC transporters HMG-CoA reductase inhibitors SLC transporters drug interactions lipid-lowering drugs