阿米卡星在严重败血症患者体内的药代动力学研究

Amikacin pharmacokinetics in critically ill patients

目的初步探讨25 mg·kg-1的阿米卡星在重症监护室(ICU)患者体内的药代动力学。方法纳入符合条件的30例革兰阴性(G-)败血症患者进行阿米卡星药物治疗研究,通过非房室模型计算每名患者的阿米卡星的药代动力学。结果阿米卡星在G-败血症患者体内平均药物分布为(0.36±0.07)L·kg-1,平均血液清除率为(3.88±0.97)m L·min-1·kg-1。肌酐清除率与血清肌酸酐(SCr)相关性具有统计学意义。结论对ICU患者应用高剂量阿米卡星(≥25 mg·kg-1)需要考虑败血症对血液动力学的影响,需要密切监测败血症血液药物浓度变化,关键要考虑到重症患者体内药代动力学与普通人群是不同的。

Objective To examine the relationship between amikacin disposition kinetics after a 25 mg·kg^- 1loading dose and hemodynamic response to sepsis,as well as clinical parameters,in a population of critically ill patients. Methods In this research,30 patients who were candidate to amikacin therapy following Gram negative sepsis were enrolled. The pharmacokinetic profile of amikacin by a non-compartmental model was calculated for each patient. Results Mean volume of distribution was（ 0. 36 ± 0. 07） L·kg^- 1and mean serum amikacin clearance was（ 3. 88 ± 0. 97） mL·min^- 1·kg^- 1. In the case of Vd,APACHE II score correlation was significant. In the case of amikacin clearance,correlation between two covariates including creatinine clearance and SCr was found significant.Conclusions It appears necessary to use higher amikacin dosage（ ≥ 25 mg·kg^- 1） considering hemodynamic response of patients to sepsis. To achieve therapeutic drug concentration a close drug monitoring and a shift from the population mean toward a value more representative of the critically ill patient subpopulation is crucial.