An update on efflux and uptake transporters as determinants of statin response.
Expert Opin Drug Metab Toxicol
; 14(6): 613-624, 2018 Jun.
Article
en En
| MEDLINE
| ID: mdl-29842801
ABSTRACT
INTRODUCTION:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Hidroximetilglutaril-CoA Reductasas
/
Transportador 1 de Anión Orgánico Específico del Hígado
/
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2
/
Proteínas de Neoplasias
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Drug Metab Toxicol
Asunto de la revista:
METABOLISMO
/
TOXICOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Brasil