The ABCG2 transporter and its relations with the pharmacokinetics, drug interaction and lipid-lowering effects of statins

Abstract

The impact of the ABCG2 421C>A polymorphism on the disposition of the statins varies between different drugs and the effect on systemic exposure was greater in the case of rosuvastatin than other statins. This genetic variant was associated with greater low-density lipoprotein cholesterol response to rosuvastatin in Chinese and caucasian patients. The effect of the ABCG2 421C>A polymorphism on the lipid response to other substrate statins and clinical outcomes need to be evaluated in future studies.

Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma

“…Recent studies reported an association of ABCG2 expression with the prognosis and survival of cancer patients [22e24]. Moreover, a significant association between increased cholesterol levels and ABCG2 mRNA expression was observed [25]. To the best of our knowledge, there has been no reported study that has examined the role of ABCG2 mRNA expression induced by cholesterol in vitro in lung adenocarcinoma treatment.…”

Effect of posaconazole on the pharmacokinetics of simvastatin and midazolam in healthy volunteers

“…It was once believed that CYP3A4 as an oxidizing isozyme was the only key determinant whether plasma exposure to a given statin would change enough to represent a safety concern. More recently, several transporters of the organic anion transport series (e.g., OATP1B1 and OATP1B3) [37] have been shown to impact plasma exposure to and disposition between compartments of certain members of the statin class of drugs (e.g., pravastatin and pitavastatin). The goal of this area of research is to better understand the different stages of co-administered drugs' absorption, distribution, metabolism and elimination and the degree to which they interact as they participate in Phase I or II reactions.…”

The farnesoid X receptor -1G>T polymorphism influences the lipid response to rosuvastatin

“…Rosuvastatin is excreted mostly unchanged into the bile; therefore, interactions with hepatic apical effl ux transporters may infl uence its lipid-lowering effi cacy in the liver. There is convincing evidence showing that human ABCG2 is the major determinant of the pharmacokinetics and lipid-lowering effect of rosuvastatin ( 5 ). In addition, it has been suggested that another effl ux transporter, ABCC2, is involved in the biliary excretion of rosuvastatin in humans ( 18 ), whereas animal studies in rats identifi ed a possible role of bile acid export pump (Bsep) in the biliary clearance of rosuvastatin ( 29 ).…”