Lee Edmund, Ryan Stephen, Birmingham Bruce, Zalikowski Julie, March Ruth, Ambrose Helen, Moore Rachael, Lee Caroline, Chen Yusong, Schneck Dennis
National University Hospital and Changi General Hospital, Singapore.
Clin Pharmacol Ther. 2005 Oct;78(4):330-41. doi: 10.1016/j.clpt.2005.06.013.
Systemic exposure to rosuvastatin had been observed to be approximately 2-fold higher in Japanese subjects living in Japan compared with white subjects in Western Europe or the United States. The organic anion transporting polypeptide 1B1 contributes to the hepatic uptake of rosuvastatin. Polymorphisms in the SLCO1B1 gene can lead to reduced transport function in vitro (T 521>C). This study was conducted to determine whether the pharmacokinetic differences between Japanese and white subjects extended to other Asian ethnic groups and to determine whether polymorphisms in the SLCO1B1 gene contribute to any pharmacokinetic differences observed.
Rosuvastatin pharmacokinetics was studied in an open-label, parallel-group, single-oral dose (40 mg) study in 36 white, 36 Chinese, 35 Malay, and 35 Asian-Indian subjects living in Singapore, Singapore. Plasma concentrations of rosuvastatin and metabolites were determined by HPLC-mass spectrophotometry. Two SLCO1B1 polymorphisms (A 388>G and T 521>C) were genotyped.
Ratios for rosuvastatin area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration were 2.31, 1.91, and 1.63 and ratios for maximum plasma concentration were 2.36, 2.00, and 1.68 in Chinese, Malay, and Asian-Indian subjects, respectively, compared with white subjects. Similar increases in exposure to N-desmethyl rosuvastatin and rosuvastatin-lactone were observed. SLCO1B1 genotypes did not account for the observed pharmacokinetic differences between Asians and white subjects.
Plasma exposure to rosuvastatin and its metabolites was significantly higher in Chinese, Malay, and Asian-Indian subjects compared with white subjects living in the same environment.
据观察，与居住在西欧或美国的白人相比，居住在日本的日本受试者中瑞舒伐他汀的全身暴露量大约高2倍。有机阴离子转运多肽1B1有助于瑞舒伐他汀的肝脏摄取。溶质载体有机阴离子转运家族1B1（SLCO1B1）基因的多态性可导致体外转运功能降低（T521>C）。进行这项研究以确定日本和白人受试者之间的药代动力学差异是否也适用于其他亚洲种族，并确定SLCO1B1基因多态性是否导致观察到的任何药代动力学差异。
在一项开放标签、平行组、单口服剂量（40mg）研究中，对居住在新加坡的36名白人、36名中国人、35名马来人和35名亚洲印度受试者进行了瑞舒伐他汀药代动力学研究。通过高效液相色谱-质谱法测定瑞舒伐他汀及其代谢物的血浆浓度。对两个SLCO1B1多态性（A388>G和T521>C）进行基因分型。
与白人受试者相比，中国、马来和亚洲印度受试者从时间0到最后可定量浓度的血浆浓度-时间曲线下瑞舒伐他汀面积比分别为2.31、1.91和1.63，最大血浆浓度比分别为2.36、2.00和1.68。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。SLCO1B1基因型不能解释观察到的亚洲人和白人受试者之间的药代动力学差异。
与生活在相同环境中的白人受试者相比，中国、马来和亚洲印度受试者中瑞舒伐他汀及其代谢物的血浆暴露量显著更高。
