SLCO1B1（有机阴离子转运多肽1B1，一种摄取转运体）和ABCG2（乳腺癌耐药蛋白，一种外排转运体）的变异等位基因与匹伐他汀在健康志愿者体内的药代动力学
SLCO1B1 (OATP1B1, an uptake transporter) and ABCG2 (BCRP, an efflux transporter) variant alleles and pharmacokinetics of pitavastatin in healthy volunteers.
作者信息
Ieiri I, Suwannakul S, Maeda K, Uchimaru H, Hashimoto K, Kimura M, Fujino H, Hirano M, Kusuhara H, Irie S, Higuchi S, Sugiyama Y
机构信息
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
出版信息
Clin Pharmacol Ther. 2007 Nov;82(5):541-7. doi: 10.1038/sj.clpt.6100190. Epub 2007 Apr 25.
To investigate the contribution of genetic polymorphisms of SLCO1B1 and ABCG2 to the pharmacokinetics of a dual substrate, pitavastatin, 2 mg of pitavastatin was administered to 38 healthy volunteers and pharmacokinetic parameters were compared among the following groups: 421C/C()1b/()1b (group 1), 421C/C()1b/()15 (group 2), 421C/C()15/()15 and 421C/A()15/()15 (group 3), 421C/A()1b/()1b (group 4), 421A/A()1b/()1b (group 5), and 421C/A()1b/()15 (group 6). In SLCO1B1, pitavastatin area under plasma concentration-time curve from 0 to 24 h (AUC(0-24)) for groups 1, 2, and 3 was 81.1+/-18.1, 144+/-32, and 250+/-57 ng h/ml, respectively, with significant differences among all three groups. In contrast to SLCO1B1, AUC(0-24) in groups 1, 4, and 5 was 81.1+/-18.1, 96.7+/-35.4, and 78.2+/-8.2 ng h/ml, respectively. Although the SLCO1B1 polymorphism was found to have a significant effect on the pharmacokinetics of pitavastatin, a nonsynonymous ABCG2 variant, 421C>A, did not appear to be associated with the altered pharmacokinetics of pitavastatin.
为研究溶质载体有机阴离子转运体1B1（SLCO1B1）和ATP结合盒转运体G2（ABCG2）基因多态性对双重底物匹伐他汀药代动力学的影响，对38名健康志愿者给予2mg匹伐他汀，并比较以下几组的药代动力学参数：421C/C（）1b/（）1b（第1组）、421C/C（）1b/（）15（第2组）、421C/C（）15/（）15和421C/A（）15/（）15（第3组）、421C/A（）1b/（）1b（第4组）、421A/A（）1b/（）1b（第5组）以及421C/A（）1b/（）15（第6组）。在SLCO1B1中，第1、2和3组匹伐他汀0至24小时血浆浓度-时间曲线下面积（AUC(0-24)）分别为81.1±18.1、144±32和250±57 ng·h/ml，三组间差异显著。与SLCO1B1相反，第1、4和5组的AUC(0-24)分别为81.1±18.1、96.7±35.4和78.2±8.2 ng·h/ml。虽然发现SLCO1B1基因多态性对匹伐他汀药代动力学有显著影响，但非同义ABCG2变体421C>A似乎与匹伐他汀药代动力学改变无关。
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