严重烧伤后阿米卡星在痂下水肿液药代动力学变化

Pharmacokinetics of amikacin in the subeschar tissue fluid following severe burns

目的探讨阿米卡星于严重烧伤患者早期单剂使用后在痂下水肿液的药代动力学变化。方法10例严重烧伤早期患者在60min内单剂匀速静脉滴注阿米卡星400mg,给药后不同时间采集痂下水肿液,利用TDx以荧光偏振免疫法测定浓度,使用3P97软件计算其相关药代动力学参数,采用SPSS10.0进行统计学处理。结果研究显示,静脉滴注400mg阿米卡星后,痂下水肿液药物浓度-时间数据以二房室模型拟合最佳,阿米卡星主要药代动力学参数:t1/2α=(4.35±1.66)h,t1/2β=(80.04±9.52)h,Vc=(13.17±1.32)L,AUC=(1802.49±285.68)μg·h·ml-1,CLs=(0.2272±0.0383)L·h-1。结论阿米卡星在严重烧伤患者痂下水肿液的总体清除率明显减少,半衰期明显延长,为正常健康者血清半衰期的(28.20￣44.78)倍,单剂使用后其有效抗菌浓度可维持24h以上,说明早期短程用药即能长时间潴留在第三间隙,在创面基底和创周形成有效的抗生素屏障,有利于防治烧伤创面侵袭性感染。

Objective To investigate the changes of pharmacokinetic parameters of amikacin in the subeschar tissue fluid （STF） in the early stage of severe burns, Methods Amikacin concentration in the STF of 10 severely burned patients were determined by fluorescence polarization immunoassay （FPIA） at different time points after intravenous amikacin infusion of the initial dose of 400 rag given within 60 min, The pharmacokinetic parameters of amikacin were measured using 3P97 program and statistically analyzed with SPSS10.0 soflware, Results and Conclusion After the initial dose of 400 rag of amlkAcin, the STF concentration-time curves of amikacin were fitted in two compartment model, The pharmacokinetic parameters of amikacin in the STF were： t1/2α（4.35± 1.66） h, t1/2β=（80.04±9.52） h, Vc=（13.17± 1.32） L, AUC=（1802.49±285.68） μg·h·ml^-1, and CLs=（0.2272±0.0383） L·h^-1, demonstrating significantly lower clearance and longer elimination half life of amlkacin in the STF following amikacin administration in early stage of severe bums. Elimination half-life ofamikacin in the STF in severely burned patients was 28,20-44,78 times longer than that in the serum of normal volunteers, and the effective inhibitory concentration of amikacin could maintain for at least 24 h, suggesting antibiotic retention in the third space after early and short-term use of potent antibiotics and formation of antibiotic barrier in the STF, which may help prevent bacterial infection of the wound.