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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Disposition of atorvastatin, rosuvastatin, and simvastatin in Oatp1b2 -/- mice and intraindividual variability in human subjects
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Disposition of atorvastatin, rosuvastatin, and simvastatin in Oatp1b2 -/- mice and intraindividual variability in human subjects

机译：Oatp1b2-/-小鼠中阿托伐他汀，瑞舒伐他汀和辛伐他汀的分布以及人类受试者的个体差异

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Response to statin therapy is often unpredictable because of variability in metabolism and transport. In the recently created organic anion transporting-polypeptide 1b2 (Oatp1b2/Slco1b2)-null mice, the investigators found significantly lower liver-to-plasma ratios compared with controls for atorvastatin (16.0 ± 5.1 vs 43.5 ± 13.7, P =.002) and rosuvastatin (15.2 ± 3.3 vs 28.4 ± 9.3, P =.03), but not simvastatin (5.2 ± 1.1 vs 6.3 ± 2.9, P =.49), following tail vein injection of 1 mg/kg of each drug. In addition, the investigators examined intraindividual variation in atorvastatin, rosuvastatin, and simvastatin pharmacokinetics in healthy human subjects in a crossover study design. Areas under the plasma concentration-time curve of atorvastatin and simvastatin acid were significantly related (Spearman r = 0.68; P =.035), whereas rosuvastatin profile was not related to atorvastatin or simvastatin exposure. Together, these results in mice and humans demonstrate that predictability of exposure to one statin based on another is dependent on the specific statin pairs and the context in which they are compared.
机译：由于他汀和新陈代谢的变化，对他汀类药物治疗的反应通常是不可预测的。在最近创建的有机阴离子转运多肽1b2（Oatp1b2 / Slco1b2）-无小鼠中，研究人员发现，与阿托伐他汀的对照组相比，肝与血浆的比例明显降低（16.0±5.1对43.5±13.7，P = .002），并且尾静脉注射每种药物1 mg / kg后，瑞舒伐他汀（15.2±3.3 vs 28.4±9.3，P = .03），而不是辛伐他汀（5.2±1.1 vs 6.3±2.9，P = .49）。此外，研究人员在一项交叉研究设计中检查了健康人受试者中阿托伐他汀，瑞舒伐他汀和辛伐他汀药代动力学的个体差异。阿托伐他汀和辛伐他汀酸的血浆浓度-时间曲线下面积显着相关（Spearman r = 0.68; P = .035），而瑞舒伐他汀谱与阿托伐他汀或辛伐他汀的暴露无关。在一起，在小鼠和人类中的这些结果表明，一种他汀类药物基于另一种他汀类药物的可预测性取决于特定的他汀类对及其比较的背景。

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