Birmingham Bruce K, Bujac Sarah R, Elsby Robert, Azumaya Connie T, Zalikowski Julie, Chen Yusong, Kim Kenneth, Ambrose Helen J
AstraZeneca, Wilmington, DE, USA,
Eur J Clin Pharmacol. 2015 Mar;71(3):329-40. doi: 10.1007/s00228-014-1800-0. Epub 2015 Jan 30.
Systemic exposure to rosuvastatin in Asian subjects living in Japan or Singapore is approximately twice that observed in Caucasian subjects in Western countries or in Singapore. This study was conducted to determine whether pharmacokinetic differences exist among the most populous Asian subgroups and Caucasian subjects in the USA.
Rosuvastatin pharmacokinetics was studied in Chinese, Filipino, Asian-Indian, Korean, Vietnamese, Japanese and Caucasian subjects residing in California. Plasma concentrations of rosuvastatin and metabolites after a single 20-mg dose were determined by mass spectrometric detection. The influence of polymorphisms in SLCO1B1 (T521>C [Val174Ala] and A388>G [Asn130Asp]) and in ABCG2 (C421>A [Gln141Lys]) on exposure to rosuvastatin was also assessed.
The average rosuvastatin area under the curve from time zero to time of last quantifiable concentration was between 64 and 84 % higher, and maximum drug concentration was between 70 and 98 % higher in East Asian subgroups compared with Caucasians. Data for Asian-Indians was intermediate to these two ethnic groups at 26 and 29 %, respectively. Similar increases in exposure to N-desmethyl rosuvastatin and rosuvastatin lactone were observed. Rosuvastatin exposure was higher in subjects carrying the SLCO1B1 521C allele compared with that in non-carriers of this allele. Similarly, exposure was higher in subjects carrying the ABCG2 421A allele compared with that in non-carriers.
Plasma exposure to rosuvastatin and its metabolites was significantly higher in Asian populations residing in the USA compared with Caucasian subjects living in the same environment. This study suggests that polymorphisms in the SLCO1B1 and ABCG2 genes contribute to the variability in rosuvastatin exposure.
居住在日本或新加坡的亚洲受试者中，瑞舒伐他汀的全身暴露量约为西方国家或新加坡白种人的两倍。本研究旨在确定美国人口最多的亚洲亚组与白种人之间是否存在药代动力学差异。
对居住在加利福尼亚州的中国、菲律宾、亚洲印度、韩国、越南、日本和白种人受试者进行瑞舒伐他汀药代动力学研究。单次服用20毫克剂量后，通过质谱检测测定瑞舒伐他汀及其代谢物的血浆浓度。还评估了溶质载体有机阴离子转运体1B1（SLCO1B1，T521>C [Val174Ala]和A388>G [Asn130Asp]）和ATP结合盒转运体G2（ABCG2，C421>A [Gln141Lys]）基因多态性对瑞舒伐他汀暴露的影响。
与白种人相比，东亚亚组从零时间到最后可定量浓度时间的瑞舒伐他汀平均曲线下面积高出64%至84%，最大药物浓度高出70%至98%。亚洲印度人的数据分别为这两个种族的中间值，分别为26%和29%。观察到N-去甲基瑞舒伐他汀和瑞舒伐他汀内酯的暴露量有类似增加。携带SLCO1B1 521C等位基因的受试者的瑞舒伐他汀暴露量高于该等位基因的非携带者。同样，携带ABCG2 421A等位基因的受试者的暴露量高于非携带者。
与生活在相同环境中的白种人相比，居住在美国的亚洲人群中瑞舒伐他汀及其代谢物的血浆暴露量显著更高。本研究表明，SLCO1B1和ABCG2基因的多态性导致了瑞舒伐他汀暴露的变异性。
