【摘要】 目的 探讨大面积严重烧伤患者休克期应用亚胺培南后血液及水泡液中的药物浓度，进一步研究其药代动力学特点。方法 选取自 2016 年 6 月至 2020 年 9 月北京积水潭医院收治的 32 例烧伤面积≥50% 的烧伤患者为研究对象。入院后 2 h 内开始给予亚胺培南 1.0 g 溶解于 100 ml 0.9% 氯化钠溶液中静脉滴注，30 min 匀速滴完，每 8 小时输注 1 次。首次用药前和首次用药完毕后 0 h、0.5 h、1.0 h、2.0 h、3.0 h、4.0 h、6.0 h、8.0 h、12.0 h、24.0 h、36.0 h 及 48.0 h 分别采集静脉血 2 ml 及水泡液 1 ml，用高效液相色谱法测定血液和水泡液中的亚胺培南浓度。采用 3P97 实用药代动力学程序自动拟合并计算药代动力学参数及处理药物浓度数据。结果 大面积烧伤患者血液及水泡液中亚胺培南浓度 - 时间数据以二房室模型拟合为最佳。血液及水泡液中的主要药代动力学参数：首次给药后的峰浓度分别为（31.30±5.44） mg/L 及（26.95±5.03） mg/L；消除相半衰期(t_1/2β)分别为（1.48±0.35） h 及（3.33±0.41） h ；曲线下面积分别为（76.66±16.17） mg/h/L 及（95.38±16.64） mg/h/L；总清除率分别为（14.60 ±3.19） L/h 及（10.06 ±2.90） L/h。与血液中比较，水泡液中的 t_1/2β明显延长，曲线下面积明显增加，而总清除率明显减少，差异均有统计学意义（P <0.05）。结论 大面积严重烧伤患者休克期应用亚胺培南后血液中的半衰期明显延长，但峰、谷浓度较正常人偏低，不同患者血液中及水泡液的药物浓度及药代动力学参数均有较大差异，临床应该尽量利用药物浓度监测，并结合大面积烧伤患者的特殊性及亚胺培南自身特点进行个体化治疗。更多还原

【Abstract】 Objective To investigate the pharmacokinetic characteristics of imipenem in blood and blister fluid of patients with severe burns in shock stage.Methods From June 2016 to September 2020,32 burn patients with burn area≥50% in Beijing Jishuitan Hospital were selected as the research subjects.Imipenem 1.0 g dissolved in 100 miniliters 0.9% sodium chloride solution was given intravenously within 2 hours after admission,and the infusion was completed at a constant speed for 30 minutes,once every 8 hours.Two mini liter of venous blood and 1 mini liter of blister fluid were collected at 0 hour,0.5 hour,1 hour,2 hours,3 hours,4 hours,6 hours,8 hours,12 hours,24 hours,36 hours and 48 hours after the first administration.The concentrations of imipenem in blood and blister fluid were determined by high performance liquid chromatography.Pharmacokinetic parameters and drug concentration data were calculated automatically by 3P97 practical pharmacokinetic program.Results The concentration-time data of imipenem in blood and blister fluid of patients with extensive burn were best fitted by the two-compartment model.The main pharmacokinetic parameters in blood and vesicular fluid were(31.30±5.44) mg/L and(26.95±5.03) mg/L after first administration,respectively.The half-lives of the elimination phase(t1/2β) in blood and vesicular fluid were(1.48±0.35) hours and(3.33±0.41) hours,respectively.The areas under of curve in blood and vesicular fluid were(76.66±16.17) mg/h/L and(95.38±16.64) mg/h/L,respectively.The total clearance rates in blood and vesicular fluid were(14.60±3.19) L/h and(10.06±2.90) L/h,respectively.Compared with blood,t1/2β in vesicular fluid was significantly prolonged,the area under the curve was significantly increased,and the total clearance rate was significantly decreased,with statistical significance(P<0.05).Conclusion The half-life in blood of patients with large area severe burns is significantly prolonged after imipenem is applied in shock stage,but the peak and trough concentrations are lower than those of normal people.The drug concentration and pharmacokinetic parameters in blood and blister fluid of different patients are significantly different.Therefore,drug concentration monitoring should be used as far as possible clinically.Combined with the particularity of large area burn patients and their own characteristics of imipenem personalized treatment.更多还原