褪黑素在正常大鼠和佐剂性关节炎大鼠体内的药动学

Pharmacokinetics of melatonin in healthy rats and rats with adjuvant arthritis

目的:建立测定大鼠血浆中褪黑素(melatonin,MT)含量的高效液相色谱法(荧光检测),比较正常大鼠及佐剂性关节炎(adjuvant arthritis,AA)模型大鼠灌胃给予MT的药动学特点。方法:分别测定正常大鼠和AA模型大鼠组在不同时间点的血药浓度,将血药浓度-时间(C-t)数据经DAS ver 2.0软件处理,进行药动学参数计算,并对正常大鼠与AA大鼠组进行比较。结果:与正常大鼠组相比,AA模型大鼠10,100μg.kg-1组Cmax,AUC和MRT均显著升高,Tmax,CL/F和Vss/F均显著降低;AA模型大鼠1 000μg.kg-1组Cmax和t1/2显著升高,Tmax,Vss/F,AUC和MRT均显著降低。结论:AA模型大鼠灌胃给予MT 10和100μg.kg-1后,药物吸收速度、吸收总量显著提高,平均滞留时间显著延长。AA模型大鼠灌胃给予MT1 000μg.kg-1后,药物吸收总量下降,平均滞留时间缩短。

Objective： To establish a high performance liquid chromatography （HPLC） method for analyzing the concentration of melatonin （MT） in plasma, and to compare the pharmacokinetic parameters of melatonin after intragastric （ig） MT in healthy rats and rats with adjuvant arthritis （AA）. Methods： Plasma samples were collected at various time points to measure MT after ig administration of MT in healthy and AA rats. The pharmacokinetic profiles were analyzed by plotting drug concentration versus time. Results： The pharmacokinetics after ig MT in rats was fitted to non-linear pharmacokinetics. As compared with healthy rats, the maximum concentration （Cmax）, area under the curve （AUC） and mean residence time （MRT） were significantly increased at low and moderate doses of ig MT （10 and 100μg·kg^-1） in rats with AA; the Tmax CL/F and Vss/F were significantly decreased; the C and tl/2 were further increased at high dose （1 000μg·kg^-1） , while the Tmax Vss/F, AUC and MRT were significantly decreased. Conclusion： Rate of absorption, total amount of absorption and MRT are increased after ig MT at 10 and 100μg·kg^-1 ; while total amount of absorption and MRT are decreased at 1 000μg·kg^-1 in rats with AA.