The Influence Of SLCO1B1and ABCG2Polymorphisms On The Pharmacokinetics Of Rosuvastatin

At present, rosuvastatin is the latest, most potent (3-hydroxy-3-methylglutaryl coenzyme A(HMG Co A) reductase inhibitor, used for prediction and curation of the cardiovascular diseases,have gotten good response,however,it would increasingly be in the high risk of adverse reactions including myopathy, rhabdomyolysis.Although there are many factors leading to this phenomenon, pharmacogenetic factor may be one of the most important reasons. Due to10percent of the rosuvastatin is metabolized by CYP450, most of them was excreated mainly unchanged.Therefore, active tranporters including OATP1B1and BCRP avidly transport rosuvastatin could play a vital role in drug distribution in vivo, resulting in relative drugs pharmacokinetic parameters,further explaining pharmacodymanic differences.OATP1B1is coded by gene SLCO1B1located at chromosome12p12,mainly expressed at the basolateral membrane of hepatocytes, mediates various endogenous, exogenous substances from portal ve nous blood into liver, including statins(pitavastatin,rosuvastatin,ceriva statin,simvastatin),benzylpenicillin.Methotrexate rifampicin,caspofungin, temocapril,valsartan, irinotecan,etc.SLCO1B1is the highly polymorp hic gene, and several functional polymorphisms have reported in dif ferent reports, among them,521T>C,388A>G are the most important ones, because they altered many drugs pharmacokinetics.BCRP is coded by gene ABCG2located at chromosome4q22,mainly expresses at small intestine, rectum, liver,kidney, stem cell, ovary,breast, brain, heart and tumor,could mediated many endogenous, exogenous substances including topotecan, Pitavastatin, estrogen, Rosuvastatin, Gefitinib, daunorubicin, Imatinib, Sunitinib, Mitoxantrone, Olmesartan,etc. Although lots of variants have been found,421C>A is the most important functional polymorphism in vivo and in vitro, the variant induce the transport activity and significantly influence the pharmacokinetics of drugs, even the explanation of the side reaction.Therefore, the research was to realize the influence of common variants related to SLCO1B1,ABCG2on the pharmacokinetics of rosuvastatin.The main results of the research are as bellowed:1.The frequency of the SLCO1B1T521C,SLCO1B1A388G,ABCG2C421A were10.5%、71.6%、31.6%,respectively,in relatively large scale crowd.2.The common polymorphisms of the SLCO1B1,ABCG2could influence on the pharmacokinetic parameters of rosuvastatin, and supply supports of theory and experiment evidence for individual medicine.