| Autor: |
Generaux GT; GlaxoSmithKline, Research Triangle Park, NC 27709, USA. grant.t.generaux@gsk.com, Bonomo FM, Johnson M, Doan KM |
| Jazyk: |
angličtina |
| Zdroj: |
Xenobiotica; the fate of foreign compounds in biological systems [Xenobiotica] 2011 Aug; Vol. 41 (8), pp. 639-51. Date of Electronic Publication: 2011 Mar 22. |
| DOI: |
10.3109/00498254.2011.562566 |
| Abstrakt: |
Statins are the preferred class of drugs for treating patients with atherosclerosis and related coronary heart disease. Treatment with statins leads to significant low-density lipoprotein cholesterol (LDL-C) lowering, resulting in reductions in major coronary and vascular events. Statins are generally well tolerated and safe; however, their use is complicated by infrequent, but often serious, muscular adverse events. For many statins, both efficacy and risk of adverse muscle events can be influenced by membrane transporters, which are important determinants of statin disposition. Genetic polymorphisms and drug-drug interactions (DDIs) involving organic anion-transporting polypeptide 1B1 and breast cancer resistance protein have shown the capacity to reduce the activity of these transporters, resulting in changes in LDL-C lowering by statins, as well as changes in the frequency of adverse muscle events associated with their use. This review presents evidence for how reduced transporter activity impacts the safety and pharmacology of statins. It expands on the scope of other recent statin reviews by providing recommendations on in vitro evaluation of statin interaction potential, discussing how reduced transporter activity impacts statin management during drug development, and proposing ideas on how to evaluate the impact of DDI on statin efficacy during clinical trials. Furthermore, the potential clinical consequences of perturbing statin efficacy via DDI are discussed. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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