Effect of organic anion transporting polypeptide 1B1 inhibition on the pharmacokinetics of rosuvastatin via HNF1a by ursodeoxycholic acid in vivo
作者单位：Institute of Natural Product and Clinical Pharmacology Ulm UniversityHelmholtzstrUlm 89081Germany
会议名称：《中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议》
会议日期：2007年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
关 键 词：OATP1B1 HNF1a UDCA rosuvastatin inhibition
摘 要：AIM:The inhibition of organic anion transporting polypeptide 1BI(OATPIB1)on the pharmacokinetics of rosuvastatin is ***,the effect of ursodeoxy- cholic acid(UDCA)on the kinetics of rosuvastatin in healthy volunteers is to be investigated. METHODS:The inhibition effect of long term use of UD- CA on rosuvastatin kinetics was studied in 12 subjects in a randomized,crossover *** subject received 500 mg UDCA once daily continuously for 14 days.A single oral dose of 20 mg rosuvastatin was given on study day 15 and 34 separated by 2 *** concentrations of ro- suvastatin were above the limits of quantitation for up to 72 h after dosing. RESULTS:UDCA significantly increased AUCand AUCof rosuvastatin to 146%±55%(P=0.008) and 167%±73%(P=0.004)compared with those of the control group and CL/F decreased 75%±19%(P= 0.003).The results confirmed the in vitro study that UD- CA inhibited OATP1B1 activity via hepatic nuclear factor la(HNFIa). CONCLUSION:Inhibition of HNF1 a and hepatic uptake may have consequences on clinic outcomes of drugs like rosuvastatin mainly excreted by hepatobiliary system.