羟磷灰石骨水泥/去甲万古霉素缓释系统的体内释药试验

Drug Releasing Test in vivo of Hydroxyapatite Cement/Norvancomycin as Drug Delivery System

目的研究相同剂量的羟磷灰石骨水泥 /去甲万古霉素 (HAC/NVCM)局部和全身用药 ,及全身血药浓度和局部骨药浓度的差异。方法形成兔右侧胫骨上端骨缺损模型。局部用药组 (A组 ) :在骨缺损中放入一定载药量的HAC/NVCM ,术后 0 .5、1、6、2 4、72h和 1、2周分别自耳动脉取血以及自材料植入区外围 0 .5cm取局部骨组织 ,用高效液相色谱仪检测不同时间点血清和骨组织中NVCM浓度。全身用药组 (B组 ) :放入未载药HAC ,自兔耳缘静脉注射 10 %NVCM溶液按 10mg/kg计算。术后 10min和 0 .5、1、6、2 4h分别取耳动脉血和局部用药组相同部位的骨组织 ,分别测定不同时间点血清和骨组织中NVCM浓度。结果相同的用药剂量 ,采用局部用药能获得数十倍于全身用药的局部骨药浓度且持续较长时间 ,同时全身血药浓度维持较低水平。

Objective To compare and evaluate the difference of serum and bone drug concentration between the methods of drug delivery system (DDS) and systematic injection. Methods The experimental radial bone defect models in rabbits were first prepared. Then the animals were divided into two groups. In group A with HAC/NVCM inlaid to the defects the serum drug concentrations at 0.5,1,6,24,72 h,1 w and 2 w after operation were determined. At the mean time, the local bone drug concentrations at 1 h,6 h,1 d,3 d,1 w and 2 w after operation were also determined. In group B with NVCM solution injected into the rabbit ear vein, the serum drug concentrations at 1/6 h,1/2 h,1 h,6 h,24 h postoperatively were determined, and the local bone drug concentrations at 1/6 h,1/2 h,1 h,6 h 24 h were determined too. Results DDS could provide a high local concentration level which sustained for at least two weeks, while NVCM concentration in serum was much lower at the same time.That is what we need in the treatment of chronic osteomyelitis. Conclusion DDS is a good method to treat chronic bone infection because of high local drug concentration and lasting for a long time.