替考拉宁与阿米卡星在烧伤患者痂下组织液中的药动学研究

Pharmacokinetic Study of Amikacin and Teicoplanin in Sub-eschar Tissue Fluid of Burn Patients

目的:考察替考拉宁和阿米卡星在早期严重烧伤患者痂下组织液(STF)中的药动学参数。方法:选取20名严重烧伤的患者为研究对象,在烧伤后24 h接受500mg替考拉宁(10例)或400 mg阿米卡星(10例)静脉滴注,在滴注结束后1、2、4、8、24、48、96、144、192、240 h时收集STF样品;另取健康志愿受试者12例收集血清作对照组。用TDx免疫分析仪测定样品中抗生素浓度,并计算替考拉宁和阿米卡星药动学参数。结果:STF及血清中替考拉宁和阿米卡星药-时曲线均符合两室模型。替考拉宁在STF中的药动学参数为:t1/2α(3.74±2.64)h、t1/2β(92.18±11.73)h,V c(25.64±5.68)L、AUC(1 279.42±256.12)μg·h/ml,CLs(0.404 8±0.078 8)L/h。阿米卡星在STF中的药动学参数为:t1/2α(4.35±1.66)h、t1/2β(80.04±9.52)h、V c(13.17±1.32)L,AUC(1 802.49±285.68)μg·h/ml,CLs(0.227 2±0.038 3)L/h。结论:单剂量静脉滴注结束后24h替考拉宁和阿米卡星在STF的浓度仍高于常见致病菌的最低抑菌浓度。提示在烧伤早期使用强效抗生素可在STF中获得有效而持久的抗菌浓度,有利于在创面基底和创周形成有效的抗生素屏障,防止烧伤创面感染性细菌侵入。

OBJECTIVE： To observe pharmacokinetic parameters of teicoplanin and amikacin in sub-eschar tissue fluid （STF） of the early stage of severe bum patients. METHODS： 20 patients with severe burn as subjects received 500 mg teicoplanin （10 cases） or 400 mg amikacin （10 cases） intravenously in 24 hours after injury; STF was collected at 1, 2, 4, 8, 24, 48, 96, 144, 192 and 240 h after infusion as well as serum from 12 healthy volunteers. Antibiotic concentrations in samples were determined by using TDx immunoassay analyzer, and the pharmacokinetics parameters of teicoplanin and amikacin were calculated. RESULTS： The drug con- centration-time curve for amikacin and teicoplanin in STF and blood were conformed to two-compartment model. The pharmacokinet- ic parameters of teicoplanin in STF were as follows： t1/2α（3.74 ± 2.64）h, t1/2β（92.18 ± 11.73）h, Vc （25.64±5.68） L, AUC（1 279.42 ±256.12）μg h/ml, CLs （0.404 8±0.078 8）L/h. Those of amikacin in STF were： t1/2α（4.35±1.66） h,t1/2β（80.04± 9.52）h, Vc （13.17± 1.32）L, AUC （ 1 802.49 ± 285.68）μg h/ml, CLs （0.227 2 ± 0.038 3） L/h. CONCLUSIONS： The concentrations of vancomycin and amikacin in STF are still higher than MIC of common pathogen 24 h after single dose intravenous dripping. The early use of potent antibiotics in the burn patients can obtain effective and lasting inhibitory concentrations and contribute to the formation of effective an- tibiotic barrier at wound base and around wound, so as to prevent bacterial invasion.