阿米卡星在严重烧伤患者水疱液中药物动力学研究

Study on pharmacokinetics of amikacin in blister fluid of severe burn patients

目的探讨阿米卡星在严重烧伤患者水疱液中的药物动力学参数。方法选取2008-09~2014-12广州市第一人民医院烧伤科大面积烧伤休克期32例患者按受伤后用药时间分成四组,每组8例：A组（伤后3 h用药）、B组（伤后10 h用药）、C组（伤后20 h用药）、D组（伤后30 h用药）,每例患者在30 min内静脉滴注阿米卡星400 mg。在用药后的0.25,0.5,1,2,3,4,5,6,7 h收集水疱液,用荧光偏振免疫法测定阿米卡星浓度,由DAS3.2.5软件计算药物代谢动力学参数,SPSS21.0软件进行统计分析。结果阿米卡星的主要药物代谢动力学参数如下：A组,Cmax=（12.73±1.65）μg/ml,t1/2=（1.93±0.50）h,AUC0-∞=（55.84±13.16）mg·h/L;B组,Cmax=（9.70±1.20）μg/ml,t1/2=（1.72±0.24）h,AUC0-∞=（46.73±7.15）mg·h/L;C组,Cmax=（5.95±0.63）μg/ml,t1/2=（2.49±0.76）h,AUC0-∞=（30.97±3.21）mg·h/L;D组,Cmax=（3.37±0.25）μg/ml,t1/2=（3.05±1.34）h,AUC0-∞=（18.07±3.86）mg·h/L。A、B组各时相点药物浓度值均明显高于C、D组（P〈0.05）,在D组药物浓度不能达到理想的抗菌浓度。结论严重烧伤早期越早应用抗生素,水疱液中的药物浓度和药物总量就越高,越有利于在创周形成有效的抗生素屏障,从而降低烧伤创面侵袭性感染的机会。

Objective To explore the changes of pharmacokinetic parameters of amikacin in the blister fluid of severe burn patients.Methods From September 2008 to December 2014,32 patients admitted to the First Municipal Hospital of Guangzhou Burn Unit were divided into four groups： postburn 3 h group（ n = 8）,postburn 10 h group（ n = 8）,postburn 20 h group（ n = 8）,postburn 30 h group（ n = 8）. All patients received intravenous infusion of 400 mg amikacin in 30 min. The blister fluid samples of each patient were collected at 0. 25,0. 5,1,2,3,4,5,6,7 h after infusion. Amikacin concentrations were determined by fluorescence polarization immunoassay（ FPIA）. Pharmacokinetic parameters were calculated using program package DAS3. 2. 5 and statistical analysis was performed using program package SPSS21. 0. Results The main parameters of amikacin in blister fluids were Cmax=（ 12. 73 ± 1. 65） μg / ml,t1 /2=（ 1. 93 ± 0. 50） h,AUC0- ∞=（ 55. 84 ± 13. 16） mg·h / L in postburn 3 h group; Cmax=（ 9. 70 ± 1. 20） μg / ml,t1 /2=（ 1. 72 ± 0. 24） h,AUC0- ∞=（ 46. 73 ± 7. 15） mg·h / L in postburn 10 h group; Cmax=（ 5. 95 ± 0. 63） μg / ml,t1 /2=（ 2. 49 ± 0. 76） h,AUC0- ∞=（ 30. 97± 3. 21） mg·h / L in postburn 20 h group; Cmax=（ 3. 37 ± 0. 25） μg / ml,t1 /2=（ 3. 05 ± 1. 34） h,AUC0- ∞=（ 18. 07 ± 3. 86） mg·h / L in postburn 30 h group. Compared with postburn 20 h and 30 h groups,the amikacin concentrations were significantly increased in postburn 3 h and 10 h groups at each time point（ P 〈 0. 05）. The amikacin concentration in postborn 30 h group didn’t reach the ideal antibacterial level. Conclusion The earlier amikacin is administered in severe burn patients at early stage,the higher the concentration in blister fluid would be,which could form an ＂antibiotic barrier＂and prevent the invasive infection from the burn wound.