[氯化两面针碱在兔体内的药代动力学研究]

Liu Huagang, Ye Dongmei, Huang Huixue, Wang Xibin, Li Danni

School of Pharmacology, Guang Xi Medical University, Nanning 530021, China.

Zhongguo Zhong Yao Za Zhi. 2009 Jun;34(11):1406-9.

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 i.v. administration in rabbits.

METHOD

Twelve rabbits, randomized into 2 groups , were given i.v. at the dose of 4, 6 mg x 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 x 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 i.v. of 4 and 6 mg x 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. T1/2alpha were (5.46 +/- 0.89), (4.76 +/- 0.33) min respectively, T1/2beta were (263.33 +/- 16.4), (274.71 +/- 16.52) min respectively, AUC were (46.56 +/- 1.80), (69.19 +/- 2.30) microg x min(-1) x 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 i.v. administration, the elimination of nitidine chloride is linear pharmacokinetics.

目的

建立一种高效液相色谱（HPLC）法测定血浆中氯化两面针碱的浓度，并成功应用于研究家兔静脉注射后的药代动力学。

方法

将12只家兔随机分为2组，分别静脉注射4、6mg·kg⁻¹剂量的药物。以氯霉素为内标。血浆中的氯化两面针碱用离子对试剂萃取后，采用HPLC法测定。

结果

氯化两面针碱的校准曲线在0.03～2.04mg·L⁻¹范围内呈线性。其回收率大于95%，日内和日间精密度均低于6%。家兔静脉注射4和6mg·kg⁻¹剂量后，氯化两面针碱的浓度-时间曲线符合二室模型，低剂量和高剂量组的主要药代动力学参数无显著差异，AUC值与剂量直接相关。T1/2α分别为（5.46±0.89）、（4.76±0.33）min，T1/2β分别为（263.33±16.4）、（274.71±16.52）min，AUC分别为（46.56±1.80）、（69.19±2.30）μg·min⁻¹·mL⁻¹。