Abstract

Context

Baicalein and simvastatin possess similar pharmacological activities and indications. The risk of their co-administration was unclear.

Objective

The interaction between baicalein and simvastatin was investigated to provide reference and guidance for the clinical application of the combination of these two drugs.

Materials and methods

The pharmacokinetics of simvastatin was investigated in Sprague–Dawley rats (n = 6). The rats were pre-treated with 20 mg/kg baicalein for 10 days and then administrated with 40 mg/kg simvastatin. The single administration of simvastatin was set as the control group. The rat liver microsomes were employed to assess the metabolic stability and the effect of baicalein on the activity of CYP3A4.

Results

Baicalein significantly increased the AUC_(0–t) (2018.58 ± 483.11 vs. 653.05 ± 160.10 μg/L × h) and C_max (173.69 ± 35.49 vs. 85.63 ± 13.28 μg/L) of simvastatin. The t_1/2 of simvastatin was prolonged by baicalein in vivo and in vitro. The metabolic stability of simvastatin was also improved by the co-administration of baicalein. Baicalein showed an inhibitory effect on the activity of CYP3A4 with the IC₅₀ value of 12.03 μM, which is responsible for the metabolism of simvastatin.

Discussion and conclusion

The co-administration of baicalein and simvastatin may induce drug-drug interaction through inhibiting CYP3A4. The dose of baicalein and simvastatin should be adjusted when they are co-administrated.

中文翻译：

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黄芩素通过调节CYP3A4活性抑制辛伐他汀在大鼠体内的药代动力学

摘要

语境

黄芩素和辛伐他汀具有相似的药理活性和适应症。他们共同给药的风险尚不清楚。

客观的

研究黄芩素与辛伐他汀的相互作用，为这两种药物联合应用的临床应用提供参考和指导。

材料和方法

在 Sprague-Dawley 大鼠 ( n  = 6) 中研究了辛伐他汀的药代动力学。大鼠用20mg/kg黄芩素预处理10天，然后用40mg/kg辛伐他汀给药。以辛伐他汀单次给药为对照组。大鼠肝微粒体用于评估代谢稳定性和黄芩素对CYP3A4活性的影响。

结果

黄芩素显着增加了simva的 AUC _{(0– t )} (2018.58 ± 483.11 vs. 653.05 ± 160.10 μg/L × h) 和C _max (173.69 ± 35.49 vs. 85.63 ± 13.28 μg/L) 第t _1/2辛伐他汀由黄芩素延长在体内和体外。辛伐他汀的代谢稳定性也因黄芩素的共同给药而得到改善。Baicalein 对 CYP3A4 的活性有抑制作用，IC ₅₀值为 12.03 μM，负责辛伐他汀的代谢。

讨论与结论

黄芩素与辛伐他汀合用可能通过抑制CYP3A4而引起药物相互作用。黄芩素与辛伐他汀合用时应调整剂量。