万古霉素鞘内给药的药代动力学研究  

Pharmacokinetics study of vancomycin in intrathecal administration

作　　者：徐伟光[1] 钟德泉[1] 赵展[1] 王文涛[1] 贺龙双[1] 

机构地区：[1]广东药科大学附属第一医院神经外科,广东广州510080

出　　处：《中国医药科学》2016年第21期71-73,123,共4页China Medicine And Pharmacy

基　　金：广东药学院附属第一医院联合基金(GYFYLH201325)

摘　　要：目的探讨万古霉素鞘内注射给药的药物代谢特点,对万古霉素鞘内给药的安全性进行初步评价。方法建立新西兰家兔鞘内置管动物模型,先行万古霉素药物半衰期测定,按不同剂量分三组,鞘内注入万古霉素后定时抽取脑脊液测定药物浓度,直至48h。间断给药实验动物按照注入万古霉素药物剂量分三组,每组均每日鞘内注入万古霉素一次,连续3日,每隔4h测定药物浓度,得出药物浓度曲线。结果鞘内注射高剂量组在给药4h左右浓度最高,之后逐渐下降,在16h浓度为4h最高的一半,48h已基本测不到;中低剂量组药物代谢曲线类似于高剂量组,除药物浓度峰值低于髙剤量组外,药物代谢速度似乎更快,代谢半衰期似乎更短。连续三日间断给药时,在每次给药后药物浓度呈迅速上升趋势;随着时间延长又再次下降,三组均不能维持在一个较稳定的药物浓度。结论药代动力学研究发现鞘内注射万古霉素半衰期在16h左右,釆用鞘内注射1天1次的方法,难以在脑脊液内形成稳定的药物浓度。Objective To investigate the pharmacokinetics of vancomyc in intrathecal administration, and to evaluate the safety of intrathecal administration of vancomycin. Methods Animal model of intrathecal catheterization rabbit was established. Vancomycin half-life determination was given on them. According to different doses, they were divided into three groups. After intrathecal administration of vancomycin, the drug concentration was determined by timed cerebrospinal fluid extraction until the end of 48 hours. Intermittent administration animals were divided into three groups according to the dose of vancomycin. Each group was injected vancomycin once daily for 3 days, and drug concentration was measured every 4H. Results In the high dose group, the concentration of the vancomyc reached the peak value at 4h, then decreased gradually, and the concentration of vancomyc fell to half its peak at 16 h.The vancomyc almost metabolism completely after 48 h. The vancomyc concentration-time curve of middle-dose group was basically similar to the high-dose group, but the peak was much lower than that of high-dose group, the time ofmetabolism faster. The low-dose group measured lower peak, metabolic half-life shorter. The drug concentration showed a rapid upward trend after each administration in the intermittent administration group. As time prolonged, The drug concentration decreased again, the three groups were not maintained at a more stable drug concentration.Conclusion The half-life of intrathecal injection is about 16 hours, and it is difficult to form a stable drug concentration in the cerebrospinal fluid by intermittent intrathecal injection.

关 键 词：万古霉素 鞘内注射 药代动力学 

分 类 号：R969.1[医药卫生—药理学]