苦参碱聚乳酸微球玻璃体腔内注射的药代动力学研究

目的研究苦参碱聚乳酸微球玻璃体腔注射后的药代动力学特点。方法将30只新西兰白兔随机分为10组,每组3只兔（6只眼）。除空白组外,其余各组每只眼玻璃体腔均注入苦参碱聚乳酸微球（含苦参碱4 mg）。分别在注药后10 min,2 h,1、3、7、14、21、28、35 d各处死1组动物取双侧眼球并制备玻璃体样本。应用高效液相色谱法检测玻璃体腔药物质量浓度,用DAS软件计算主要的药代动力学参数。结果玻璃体腔注入苦参碱聚乳酸微球（含苦参碱4 mg）后,药物在玻璃体内的平均滞留时间MRT=（221.64±9.70）h,半衰期t1/2=（173.77±32.33）h。缓释微球在玻璃体腔释药可达35 d以上,35 d时药物质量浓度为（121.8±34.6）μg/mL。随时间延长,药物的总体清除率稳定增加。结论玻璃体腔注入苦参碱聚乳酸微球（含苦参碱4 mg）,药物在眼内清除较慢,清除时间明显延长,在玻璃体腔内能够长时间维持较高的质量浓度,表现出良好的体内缓释性。

Study on pharmacokinetics of matrine polyactic acid microsphere after intravitreal injection

Objective The inhibitor）, effect of matrine polyactic acid microsphere （MAT-PLA-MS） on proliferative vitreoretinopathy（PVR） is associated with whether the injected drugs can maintain a high level in vitreous for longer-time duration. In order to determine the level of drug in vitreous, the pharmacokinetics of MAT-PLA-MS was examined in this study after intravitreal injection in rabbits. Methods Thirty healthy and mature New Zealand albino rabbits were randomly divided into 10 groups and 6 eyes of 3 rabbits for each. Rabbits in experimental groups received intravitreal implantation of MAT-PLA-MS （including matrine 4 rag） ,but drug did not be administrated in 3 animals of blank control group. At the 10th minutes,2nd hour, 1 st, 3 rd, 7th, 14th,21 st, 28th and 35 th day following injection, both eyes of animals in each group were removed respectively, and the vitreous specimens were obtained immediately for preparation and detection of matrine concentration by high performance liquid chromatography （HPLC）. The main parameters of pharmacokinetics were calculated through DAS pharmacokinetics software. Results After intravitreal implantation of MAT-PLA-MS,the pharmacokinetics parameters of drug were as follows： MRT = 221. 64 ±9. 70 hours,t1/2 = 173.77±32.33 hours. At 10 minutes,2 hours,1 day,3,7,14,21,28 and 35 days after intravitreal implantation of MAT-PLA-MS, the mass concentration of matrine in vitreous was （3 086.2±164.1 ）, （2 964.9 ± 223.4）,（2791.6 ±224.2）,（2303.3 ±181.5）,（1 648.4±234.2）,（882. 1±155.7）,（484.3 ±81.2）,（242.9±39.8）, （ 121.8 ±34.6 ） μg/mL respectively, and the total clearance rate of matrine was 8.96 % , 12.53 % , 17.65 % , 32.05 % , 51.31% , 73.98% ,85.71% ,92.63% and 96.41% respectively. Conclusion Microsphere-encapsulated matrine has a long half life and mean remaining period. MAT-PLA-MS can maintain an effective drug concentration and shows controlled release characteristics.