附子配伍甘草对CYP3A4体内活性的影响研究  

Effect of Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix on CYP3A4 in vivo

作　　者：张广平[1] 朱丽君[2] 周娟[2] 唐斓[2] 刘中秋[2] 叶祖光[3] 

机构地区：[1]中药复方新药开发国家工程研究中心,北京100075 [2]南方医科大学药学院,广东广州510515 [3]中国中医科学院,北京100700

出　　处：《中国中药杂志》2012年第15期2206-2209,共4页China Journal of Chinese Materia Medica

基　　金：国家重点基础研究发展计划(973)项目(2009CB522806)

摘　　要：目的:建立测定血浆中盐酸丁螺环酮的超高效液相色谱(UPLC)方法。考察附子配伍甘草对CYP3A4体内活性的影响。方法:ACQUITY UPLC BEH C18色谱柱(2.1 mm×10 mm,1.7μm);2.0 mmol.L-1醋酸铵(pH 7.4,A)-乙腈(B)梯度洗脱,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;检测波长243 nm;流速0.3 mL.min-1。结果:方法的线性范围0.078 125～20.0μg(r=0.997 5);平均回收率85.62%(RSD 6.8%,n=6)。本方法专属性好,重复性好,可用于血浆中盐酸丁螺环酮的测定。大鼠口服附子水煎液后口服盐酸丁螺环酮,盐酸丁螺环酮的AUC0-2 h比生理盐水组下降了52.8%(P<0.05),CL/F是生理盐水组的2.22倍(P<0.05)。附子配伍甘草组与生理盐水组比较无明显变化。结论:附子水煎液对大鼠CYP3A4酶有诱导作用,附子配伍甘草对大鼠CYP3A4则无明显影响,提示甘草可纠正附子对CYP3A4活性的诱导作用。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×10 mm,1.7 μm） was used for the gradient elution with a 2.0 mmol·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·min-1 at room temperature.The UV wavelenght was detected at 243 nm.The linear calibration curve ranged between 0.078 125-20.0 μg（r=0.997 5）.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·kg-1） decreased buspirone hydroxychloride AUC0-2 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.

关 键 词：附子 盐酸丁螺环酮 药动学 UPLC 

分 类 号：R285[医药卫生—中药学]