单剂口服苦参素胶囊后苦参素及其代谢物苦参碱在健康人体的药代动力学

Pharmacokinetics of oxymatrine and its metabolite matrine in healthy volunteers after oral administration of oxymatrine capsule

目的研究苦参素胶囊（抗乙肝药）在健康人体的药代动力学。方法10名健康受试者单剂量口服苦参素胶囊600nag，用液相色谱一串联质谱法同时测定血浆中苦参素及其活性代谢物苦参碱的血药浓度，用3P97软件进行数据处理。结果苦参素的血药浓度-时间过程符合一级吸收的一室模型。苦参素和苦参碱的药代动力学参数：Cmax分别为（0．54±0．15），（2．54±0．36）μg·mL^-1，tmax分别为（2.30±1．20），（12．30±2．60）h，AUC0-1。分别为（2．30±0．41），（41．42±6．38）h·μg·mL^-1，t1／2分别为（1．89±0.34），（7．94±0．49）h。苦参素的CIVF与WF分别为（300．20±43．40）L·h^-1和（799．10±239．50）L。结论口服苦参素胶囊经胃肠吸收后，消除较快；而大部分被转化为活性代谢物苦参碱。

Objective To investigate the pharmacokinetics of oxymatrine （OMT） capsules in healthy Chinese volunteers. Methods Ten male volunteers were given a single oral dose of 600 mg of OMT capsules. The concentrations of OMT and matrine（MT） in plasma were si - multaneously determined by a validated liquid chromatography tandem mass spectrometry（ LC - MS/MS） method. The pharmacokinetic parameters were calculated by 3P97 software. Results The plasma concentration time profiles of OMT was best fitted with first order absorption one - compartment models. The main pharmacokinetic parameters found for OMT and its active metabolite MT after po 600 mg OMT capsules were as follows： Cmax were （0.54±0. 150） and （2.54 ±0.36） μg · mL^-1,t1/2 were （2.30 ± 1.20） and （12.30 ±2.60） h,AUC0-t were （2.30 ± 0.41） and （41.42±6.38） h · μg·mL^-1,t1/2were （1.89±0.34） and （7.94±0.49） h, and the CL/F and V/F of OMT were （300.20 ±43.40） L · h^-1 and （799.10 ±239.50） L, respectively. Conclusion OMT is quickly absorbed and extensively metabolized to MT by intestinal bacteria in the gastrointestinal tract, when OMT capsules are taken orally.