氯化两面针碱在兔体内的药代动力学研究

目的:建立高效液相色谱法测定兔血浆中的氯化两面针碱,并研究静脉注射氯化两面针碱在兔体内的药代动力学特点.方法:12只家兔随机分为2组,分别iv氯化两面针碱4,6 mg·kg~(-1),以氯霉素为内标,离子对试剂萃取技术对血浆样品进行预处理,高效液相色谱法测定血浆药物浓度,用3p97药代动力学软件进行房室模型拟合并计算药代动力学参数.结果:氯化两面针碱在0.03～2.04 mg·L~(-1)范围内线性关系良好,低、中、高3种不同质量浓度的方法回收率>95%,日内、日间精密度RSD均<6%.家兔静脉注射氯化两面针碱后,药时曲线符合二室模型,主要药代动力学参数在4,6 mg·kg~(-1) 2个剂量组中的T_(1/2α)分别为(5.46±0.89),(4.76±0.33)min;T_(1/2β)分别为(263.33±16.34),(274.71±16.52)min,AUC分别为(46.56±1.80),(69.19±2.30)μg·min~(-1)·mL~(-1).结论:首次建立了氯化两面针碱血药浓度的高效液相色谱法,方法简便、快速,结果准确、可靠;并首次阐明了氯化两面针碱在兔体内的药代动力学特点,在此剂量范围内氯化两面针碱的消除为线性动力学.

Studies on pharmacokinetics of nitidine chloride in rabbits

Objective: A high performance liquid chromatography (HPLC) method was developed to determine the concentration of nitidine chloride in plasma and successfully applied to study pharmacokinetics after iv administration in rabbits.  Method: Twelve rabbits, randomized into 2 groups , were given iv at the dose of  4, 6 mg·kg-1 respectively. Chloramphenicol was used as an internal standard. Nitidine chloride was extracted from plasma with ion pair reagent, and was determined by HPLC.  Result: The calibration curves of nitidine chloride was linear in the range of 0.03-2.04 mg·L-1. Its recoveries were more than 95%, intra-day and inter-day precisions were lower than 6%. The concentration-time curve of nitidine chloride in rabbits after iv of 4 and 6 mg·kg-1 were shown to fit a two-compartment model, the main pharmacokinetic parameters showed no significant difference between the low and high dosage, and the AUC values are directly relative to doses. T1/2α were (5.46±0.89), (4.76±0.33) min respectively, T1/2β were (263.33±16.34), (274.71±16.52) min respectively, AUC were (46.56±1.80), (69.19±2.30) μg·min-1·mL-1 respectively.  Conclusion: It is first time to establish the HPLC method to determine the concentration of nitidine chloride in rabbits plasma. The method is sensitive, accurate and reproducible. It is first time to study the pharmacokinetic characters of nitidine chloride in rabbits after iv administration,the elimination of nitidine chloride is linear pharmacokinetics.