尼可胺在大鼠体内的药代动力学研究

Study on pharmacokinetics of NiKeAn in rat

    摘要
  • 摘要:
    目的 采用高效液相色谱法（HPLC）研究尼可胺在大鼠体内的药代动力学变化。
    方法 色谱柱为Sino chrom BDS柱（250 mm×4.6 mm，5 μm），流动相为甲醇-0.02%醋酸（10:90），检测波长为260 nm，柱温为30 ℃，流速为1 ml/min，进样量为5 μl。通过大鼠眼底静脉取血，血浆经乙腈沉淀蛋白，测定尼可胺血药浓度，通过DAS2.0计算其药代动力学参数。
    结果 尼可胺的线性范围：20~1000 μg/ml（r=0.9998）。当尼可胺在大鼠血浆中的浓度为50、150和500 μg/ml时，提取回收率分别为84.9%、81.9%和79.1%，批内精密度和批间精密度均＜5%。当大鼠给予125 mg/kg的尼可胺后，其主要药代动力学参数为：消除相半衰期（t1/2β）为（32.99±23.14）min，血药-时间浓度曲线下面积（AUC）（0-t）为（14390.23±2584.02）mg·L-1·min，AUC（0-∞）为（16569.89±3450.31）mg·L-1·min，达峰时间（Tmax）为（27.0±6.7）min，药峰浓度（Cmax）为（242.13±33.89）mg/L。当大鼠给予250 mg/kg的尼可胺后，其主要药代动力学参数为：t1/2β为（59.05±16.34）min，AUC（0-t）为（26752.23±7967.03）mg·L-1·min，AUC（0-∞）为（35812.87±9476.48）mg·L-1·min，Tmax为（27.5±11.3）min，Cmax为（316.32±63.68）mg/L。当大鼠给予500 mg/kg的尼可胺后，其主要药代动力学参数为：t1/2β为（69.06±0.62）min，AUC（0-t）为（77306.48±27878.03）mg·L-1·min，AUC（0-∞）为（88014.22±26960.89）mg·L-1·min，Tmax为（40.0±7.7）min，Cmax为（601.42±147.150）mg/L。
    结论 HPLC操作简便、准确、灵敏度高、重现性好，能够用于尼可胺在大鼠体内的药代动力学研究，为人体内尼可胺的药代动力学研究提供了参考。

     

    Abstract:
    Objective To develop a sensitive and specific high performance liquid chromatography(HPLC)method for determination of NiKeAn in rat plasma, and study the Pharmacokinetics in rat.
    Methods Sino chrom BDS column(250 mm×416 mm, 5 μm)was used. The mobile phase was CH3OH-0.02%-phosphoric acid(10:90)with a flow rate of 1.0 ml/min, and the detection wave length was at 260 nm and 30 ℃ column temperature. The plasma was analyzed after a simple protein precipitation procedure with acetonitrile. The blood sample was collected from retinal vein and involved protein precipitation with acetonitrile. Concentration of NiKeAn in rat blood was analyzed by the established method, and the pharmacokinetics parameters were calculated by the DAS2.0 software.
    Results The linear range of NiKeAn in rat plasma was 20-1000 μg/ml(r=0.9998). As concentration of NiKeAn in rat plasma were 50, 150 and 500 μg/ml, the relative standard deviation of intra-batch and inter-batch were both less than 5.0%. The recovery rates of NiKeAn were 84.9%, 81.9% and 79.1%, respectively. After single dose of 125 mg/kg in rat, the main pharmacokinetic parameters were estimated to be as follows: elimination half-life time(t1/2β)was(32.99±23.14)min, the area under the curve(AUC)(0-t)was(14390.23±2584.02)mg·L-1·min, AUC(0-∞)was(16569.89±3450.31)mg·L-1·min, the time of peak(Tmax)was(27.0±6.7)min, the peak concentration of drug(Cmax) was(242.13±33.89)mg/L. After single dose of 250 mg/kg in rat, the main pharmacokinetic parameters were estimated to be as follows: t1/2β was(59.05±16.34)min, AUC(0-t)was(26752.23±7967.03)mg·L-1·min, AUC(0-∞)was(35812.87±9476.48)mg·L-1·min, Tmax was(27.5±11.3)min, Cmax was(316.32±63.68)mg/L. After single dose of 500 mg/kg in rat, the main pharmacokinetic parameters were estimated to be as follows: t1/2β was(69.06±0.62)min, AUC(0-t)was(77306.48±27878.03) mg·L-1·min, AUC(0-∞)was(88014.22±26960.89)mg·L-1·min, Tmax was(40.0±7.7)min, Cmax was(601.42±147.15)mg/L.
    Conclusions The operation of established HPLC approach was simple, accurate, high-sensitive and better reproducible. This study provides a better reference for pharmacokinetics of NiKeAn in human bodies.

     

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