来源：风湿病与关节炎,2017,6（12）:38-41,53.

骨痹舒片中马钱子碱和士的宁在大鼠体内的药动学研究（药物研究）

张景姣，杨艳娇，祁利平，董艳艳，张　健，李瑞柯，刘雅敏

　　【摘　要】目的：以制马钱子粉为参照，研究骨痹舒片中马钱子碱和士的宁在大鼠体内的药动学特征。方法：大鼠单次灌胃给予骨痹舒片和制马钱子粉，采用尾静脉采血技术，以盐酸克伦特罗为内标，超高液相色谱-质谱联用法测定大鼠血浆中马钱子碱和士的宁浓度，DAS 3.0软件计算药动学参数。结果：骨痹舒片中马钱子碱和士的宁的分别为27.5 min、37.5 min，为5.467 ng·mL^-1、22.483 ng·mL^-1，_→t为879.501 ng·min^-1·L^-1、4 105.627 ng·min^-1·L^-1，t_1/2α为25.849 min、30.6 min，t_1/2β为285.299 min、154.2 min；CL/F为4 205.938 L·min^-1·kg^-1、654.955 L·min^-1·kg^-1。结论：马钱子碱和士的宁在大鼠体内的药动学过程均符合二房室模型。两者在骨痹舒片中具有快吸收、快分布、快消除的药动学特征。与制马钱子粉相比，骨痹舒片中马钱子碱的生物利用度增加59.9倍，士的宁的生物利用度增加27.0倍，且吸收和消除速度均显著高于制马钱子粉，提示骨痹舒片中其他配伍药味或制剂工艺对制马钱子的体内过程有影响。临床给药时，若给药剂量过高，会较快出现药效及毒性反应，但药效维持时间较短。

　　【关键词】　马钱子碱；士的宁；骨痹舒片；药动学；超高液相色谱-质谱联用法；大鼠

Pharmacokinetic Study on Brucine and Strychnine in Gubishu Pian（骨痹舒片）in Rats

ZHANG Jing-jiao,YANG Yan-jiao,QI Li-ping,DONG Yan-yan,ZHANG Jian,LI Rui-ke,LIU Ya-min

　　【ABSTRACT】 Objective:Take Maqianzi powder as reference to make a pharmacokinetic study on brucine and strychnine in Gubishu Pian（骨痹舒片）in rats.Methods:Rats were given intragastric administration of Gubishu Pian and processed Maqianzi powder,collecting blood from tail vein.With Clenbuterol as the internal standard,UPLC-MS/MS was used to determine the concentrations of brucine and strychnine in plasma of rats.Software DAS 3.0 was used to calculate pharmacokinetic parameters.Results:In Gubishu Pian,the parameters of brucine and strychnine were as follows:（27.5 min,37.5 min）;（5.467 ng·mL^-1,22.483 ng·mL^-1）;AUC_→t（879.501 ng·min^-1·L^-1,4 105.627 ng·min^-1·L^-1）;t_1/2α（25.849 min,30.6 min）;t_1/2β（285.299 min,154.2 min）;CL/F（4205.938 L·min^-1·kg^-1,654.955 L·min^-1·kg^-1）.Conclusion:The pharmacokinetic processes of brucine and strychnine in rats in vivo are in line with the two compartment model.Both of them have the pharmacokinetic characteristics of fast absorption,fast distribution and fast elimination in Gubishu Pian.Compared with processed Maqianzi powder,the bioavailability of brucine in Gubishu Pian has increased by 59.9 times,the bioavailability of strychnine has increased by 27.0 times,and the absorption and elimination rates were significantly higher than that of processed Maqianzi powder,which suggests that other compatible medicinal in Gubishu Pian or other preparation technologies have effects on the process of processed Maqianzi in vivo.In clinical administration,high dosage of it will cause quick drug efficacy and toxic reaction,with short duration.

【Keywords】 brucine;strychnine;Gubishu Pian（骨痹舒片）;pharmacokinetics;UPLC-MS/MS;rats