载万古霉素人工骨微球的人体局部释放及全身药物浓度监测

Local release of vancomycin-loaded artificial bone in human and monitoring of drug concentration

目的通过测定载万古霉素人工骨微球植入骨感染患者体内后全身及局部的药物浓度,了解万古霉素人工骨的释放规律,为临床使用万古霉素人工骨治疗骨感染提供依据。方法 2017年1-7月收治的骨感染患者13例,手术时在局部感染灶植入2 g万古霉素与硫酸钙人工骨混合制成的药物微球,术中局部埋置引流管,分别于术后2 h及此后每日清晨留取患者静脉血及伤口引流液标本,直至术后引流管拔除。使用酶放大免疫法进行静脉血及引流液万古霉素浓度测定。结果 13例患者中,男11例,女2例,平均年龄(41.93±14.39)岁,引流管留置时间中位数为3 d,血药峰浓度为1.68μg/m L,达峰时间为16.09 h,局部释放率最高峰值出现在9 h,最大释放速率为28.72 mg/h。累计局部释放率为23.06%,溶出模型拟合符合Weibull方程,r=0.966 8。结论局部植入万古霉素硫酸钙人工骨微球可以至少在术后1周内伤口局部达到很高的药物治疗浓度,而全身药物浓度很低,可以避免全身使用万古霉素带来的不良反应,具有很高的安全性。

Objective To evaluate the release of vancomycin-loaded artificial bone by measuring the systemic and local drug concentration in patients implanted with vancomycin-loaded artificial bone in order to provide proof for the treatment of bone infection. Methods Thirteen patients with bone infections from January to July in 2017 were treated with artificial bone of 2 g vancomycin combined with calcium sulphate at the local infection of bone. The local- ized drainage tube was implanted. The venous blood and wound drainage fluid specimens was taken at 2 h after opera- tion and every morning,till the drainage tubes were removed. Enzyme amplification immunoassay was used to deter- mine the concentration of vancomycin in venous blood and drainage fluid. Results The 13 patients averaged （41.93± 14. 39） years old with 11 males and 2 females. The median time of drainage was 3 days,CmaX was 1.68 μg/mL,TmaX was 16. 09 h, the highest peak rate appeared at the 9th hour, and the maximum release rate was 28.72 mg/h. The cumulative local release rate was 23.06% , and the dissolution model was fitted to the Weibull equation （r =0. 966 8 ）. Conclusion Local implantation of vancomycin in calcium sulfate artificial bone microspheres can achieve a high concen- tration of drug in the wound for at least a week after operation, with low systemic drug blood concentration and high safety, which avoids the systemic adverse reactions.