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目的用超高效液相色谱-质谱联用(UHPLC-MS/MS)技术研究黄芪注射液(RA)对大鼠细胞色素P450(CYP)2D6、2C19、3A4、1A2和2C9活性的影响。方法按照体重将SD大鼠分为对照组和实验组,对照组腹腔注射0.9%NaCl,实验组腹腔注射RA 10 mL·kg~(-1),连续给药7 d。最后一次给药30 min后,2组均一次性灌胃探针药(美托洛尔、奥美拉唑、咪达唑仑、非那西汀和甲苯磺丁脲)。在不同时间点采血,进行UHPLC-MS/MS分析,计算5个探针药的药代动力学参数。以5个探针药的药代动力学评价CYP2D6、2C19、3A4、1A2和2C9活性。结果与对照组比较,美托洛尔、奥美拉唑、非那西汀和甲苯磺丁脲于实验组的AUC0-t分别下降了37.8%,55.5%,40.9%,38.9%,C_(max)分别下降了25.4%,33.6%,14.6%,40.2%;而咪达唑仑于实验组的AUC_(0-t)和C_(max)分别显著增加了60.1%和195%。表明RA可增强咪达唑仑血浆吸收量而减弱美托洛尔、奥美拉唑、非那西汀和甲苯磺丁脲吸收量。结论 RA可抑制CYP3A4酶活性,而诱导CYP2D6、2C19、1A2和2C9酶活性。
Objective To investigate the effect of astragalus injection on the activities of cytochrome P450 (CYP) 2D6, 2C19, 3A4, 1A2 and 2C9 in rats by ultra performance liquid chromatography-mass spectrometry (UHPLC-MS / MS) Methods According to body weight, SD rats were divided into control group and experimental group. The control group received 0.9% NaCl intraperitoneal injection. The experimental group received intraperitoneal injection of RA 10 mL · kg ~ (-1) for 7 days. After the last administration for 30 min, the two groups were given a single oral probe (metoprolol, omeprazole, midazolam, phenacetin and tolbutamide). Blood samples were taken at different time points and subjected to UHPLC-MS / MS analysis to calculate the pharmacokinetic parameters of the 5 probe drugs. The CYP2D6, 2C19, 3A4, 1A2 and 2C9 activities were evaluated by pharmacokinetics of 5 probe drugs. Results Compared with the control group, metoprolol, omeprazole, phenacetin and tolbutamide decreased 37.8%, 55.5%, 40.9%, 38.9% and C_ (max) in the experimental group ) Decreased by 25.4%, 33.6%, 14.6% and 40.2% respectively; while the midazolam significantly increased the AUC_ (0-t) and C_max of the experimental group by 60.1% and 195% respectively. This suggests that RA increases the plasma absorption of midazolam and attenuates the absorption of metoprolol, omeprazole, phenacetin, and tolbutamide. Conclusion RA inhibits CYP3A4 activity and induces CYP2D6, 2C19, 1A2 and 2C9 activities.