[附子与甘草配伍对体内CYP3A4的影响]

[Effect of aconiti laterlis radix compatibility of glycyrrhizae radix on CYP3A4 in vivo].

作者信息

Zhang Guangping, Zhu Lijun, Zhou Juan, Tang Lan, Liu Zhongqiu, Ye Zuguang

机构信息

National Engineering Research Center for Traditional Chinese Medicine Compound Drug Development, Beijing 100075, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2012 Aug;37(15):2206-9.

PMID:23189719

Abstract

The primary objective was to develope a UPLC method for determine the concentration of buspirone hydroxychloride in plasma and to evaluate the effects of Aconiti Laterlis Radix and Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix on CYP3A4 in vivo. ACQUITY UPLC BEH C18 column (2.1 mm x 10 mm, 1.7 microm) was used for the gradient elution with a 2.0 mmol x L(-1) ammonium acetate (pH 7.4, A)-acetonitrile (B) solution, 0-2.2 min, 10% - 60% B, 2.2-2.5 min, 60% B, 2.5-3.0 min, 60%-75% B, 3.0-3.5 min, 75% B, 3.5-4.0 min, 75%-10% B, at the flow rate of 0.3 mL x min(-1) at room temperature. The UV wavelenght was detected at 243 nm. The linear calibration curve ranged between 0.078 125-20.0 microg (r = 0.9975). The average recovery (n = 6) of buspirone hydroxychloride was 85.62% (RSD 6.8%). The results showed that this method has good specificity and repeatability, and which can be used for the determination of buspirone hydrochlorid in serum. In animial studies, single dose Aconiti Laterlis Radix extract treatment (0.5 g x kg(-1)) decreased buspirone hydroxychloride AUC(0-2 h) (52.8%, P = 0.020), increased CL/F (122%, P = 0.045). Compared to the saline treatment group, Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract treatment has no effect on CYP3A4 in rat. The results indicated that Aconiti Laterlis Radix extract induced CYP3A4 while Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract had no effect on CYP3A4 in vivo. Aconiti Laterlis Radix had been detoxified when be used as compatibility of Glycyrrhizae Radix.

摘要

主要目的是开发一种超高效液相色谱（UPLC）方法，用于测定血浆中盐酸丁螺环酮的浓度，并评估附子及附子与甘草配伍对体内细胞色素P450 3A4（CYP3A4）的影响。采用ACQUITY UPLC BEH C18色谱柱（2.1 mm×10 mm，1.7 µm），以2.0 mmol·L⁻¹醋酸铵（pH 7.4，A）-乙腈（B）溶液进行梯度洗脱，0 - 2.2分钟，10% - 60% B；2.2 - 2.5分钟，60% B；2.5 - 3.0分钟，60% - 75% B；3.0 - 3.5分钟，75% B；3.5 - 4.0分钟，75% - 10% B，室温下流速为0.3 mL·min⁻¹。紫外波长检测为243 nm。线性校准曲线范围为0.078 125 - 20.0 µg（r = 0.9975）。盐酸丁螺环酮的平均回收率（n = 6）为85.62%（相对标准偏差6.8%）。结果表明，该方法具有良好的特异性和重复性，可用于血清中盐酸丁螺环酮的测定。在动物研究中，单剂量附子提取物处理（0.5 g·kg⁻¹）降低了盐酸丁螺环酮的药时曲线下面积（AUC₀ - ₂h）（52.8%，P = 0.020），增加了清除率（CL/F）（122%，P = 0.045）。与生理盐水处理组相比，附子与甘草配伍提取物处理对大鼠的CYP3A4无影响。结果表明，附子提取物诱导CYP3A4，而附子与甘草配伍提取物在体内对CYP3A4无影响。附子与甘草配伍时已解毒。