目的 研究辣椒素对辛伐他汀血浆蛋白结合率的影响。方法 采用超滤法结合液相色谱-质谱联用法(LC-MS/MS),对未加和加入辣椒素后辛伐他汀与大鼠及健康人血浆的蛋白结合率进行测定。结果 在0.2,0.5,1 μg·mL-1质量浓度下辛伐他汀与大鼠血浆的蛋白结合率分别为:(97.73±0.24)%,(96.75±2.58)和(96.23±0.81)%;与健康人血浆的蛋白结合率分别为:(97.05±1.74)%,(97.68±0.65)%和(97.20±1.00)%。当合并加入辣椒素(1 μg·mL-1)后,血浆蛋白结合率分别下降至:(93.97±0.96)%,(92.76±1.89)%,(92.05±0.58)%和(91.71±2.51)%,(91.73±1.88)%,(91.41±2.48)%;同时游离的药物浓度分别增加了1.66,1.23,1.11倍和1.81,2.56,2.07倍。结论 辣椒素能够使辛伐他汀的血浆蛋白结合率显著降低,使其游离型药物浓度显著升高(P<0.01)。临床运用辛伐他汀时,应注意联用含有辣椒素的药物/食物对其血浆蛋白结合率的影响。
Abstract
OBJECTIVE To investigate the effect of capsaicin on the binding rates of simvastatin with rats and healthy subjects plasma. METHODS The plasma protein binding rates of simvastatin in the presence or absence of capsaicin were determined by ultrafiltration combined with liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS The binding rates of simvastatin (0.2, 0.5, 1 μg·mL-1) were (97.73±0.24)%, (96.75±2.58)%, and (96.23±0.81)% in rat plasma and (97.05±1.74)%, (97.68±0.65)%, and (97.20±1.00)% in human plasma, respectively. In the presence of capsaicin (1 μg·mL-1), the plasma protein binding rates of simvastatin decreased to (93.97±0.96)%, (92.76±1.89)%, (92.05±0.58)% and (91.71±2.51)%, (91.73±1.88)%, (91.41±2.48)%, while the unbound drug concentration increased by 1.66, 1.23, 1.11 fold and 1.81, 2.56, 2.07 fold, respectively. CONCLUSION Capsaicin could significantly decrease the plasma protein binding rate of simvastatin and increase its free drug concentration (P<0.01). When the clinical use of simvastatin, attention should be paid to the effect of drugs/ food containing capsaicin on its plasma protein binding rate.
关键词
辛伐他汀 /
辣椒素 /
血浆蛋白结合率 /
超滤法 /
药物相互作用
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Key words
simvastatin /
capsaicin /
plasma protein binding rate /
ultrafiltration /
drug interaction
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中图分类号：
R969.2
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参考文献
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脚注
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基金
国家自然科学基金资助项目(81473287, 81403012)
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