Objective To investigate the effects of different modes of imipenem-cilastatin sodium infusion on pharmacokinetics and pharmacodynamics in patients with severe pneumonia.Methods Fifty-six patients with severe pneumonia were randomly divided into two groups,with 28 patients in each group.Patients in experimental group were given constant intravenous infusion of imipenem-cilastatin sodium 250 mg for 30 minutes and intravenous infusion of imipenem-cilastatin sodium 750 mg for 2.5 hours(imipenem-cilastatin sodium 1 g was dissolved in 100 mL of 0.9% sodium chloride injection) every 8 hours.Patients in control group were given constant intravenous infusion of imipenem-cilastatin sodium 1 g in 100 mL of 0.9% sodium chloride injection for 60 minutes every 8 hours.Blood samples(2 mL) were drawn from the radial arteries after administration for 48 hours,before re-administration,and 1,2,3,4,6 and 8 hours after re-administration.Plasma concentrations of imipenem were determined by high performance liquid chromatography and the pharmacokinetic parameters were calculated using the DAS 3.0 soft.In addition,the percentage of the time above four times of the MIC(%T>4×MIC) was calculated according to the concentration-time curves.Results Calibration curves of imipenem showed good linear regression in the range of 0.5-100 mg·L-1(r=0.999 7).The lower limit of quantification of imipenem was 0.5 mg·L-1.Compared with experimental group,the Cmax of imipenem increased and the Cmix of imipenem decreased in control group(P<0.01).There were no significant differences in the AUC0-∞,t1/2,kel,CLtot,Vd and Vd·kg-1 between the two groups(P>0.05).At the MIC of 0.5,1 and 2 mg·L-1,the %T>4×MIC in experimental group was higher than that in control group(P<0.01).At the MIC of 4 mg·L-1,the %T>4×MIC was less than 40% in both groups and the difference was not significant between the two groups(P>0.05).Conclusion Prolonged infusion of imipenem-cilastatin sodium can increase the %T>4×MIC in patients with severe pneumonia.Furthermore,the %T>4×MIC shows a downward trend with the increase in MIC.Both drug infusion modes cannot achieve a good bactericidal effect at the MIC≥4 mg·L-1.Therefore,the dosages of imipenem-cilastatin sodium should be increased or other antimicrobial agents should be used for the treatment of severe pneumonia.%目的 探讨亚胺培南-西司他丁钠不同给药方式对重症肺炎患者药代动力学及药效学的影响.方法 将56例重症肺炎患者按随机数字表法分为试验组和对照组,每组28例.试验组采用注射用亚胺培南-西司他丁钠1.0 g加入0.9%氯化钠注射液100 mL,其中250 mg匀速静脉滴注30 min,750 mg静脉滴注2.5 h,每8 h 1次.对照组采用注射用亚胺培南-西司他丁钠1.0 g加入0.9%氯化钠注射液100 mL中匀速静脉滴注60 min,每8 h 1次.用药48 h后,在再次给药前及再次给药后 1、2、3、4、6、8 h 经桡动脉导管取血2 mL,使用高效液相色谱法检测血浆亚胺培南的浓度,采用DAS 3.0药代动力学软件计算2组患者血浆亚胺培南的药代动力学参数(Cmax、Cmix、AUC0-∞、t1/2、kel、CLtot、Vd、Vd·kg-1);根据药物浓度绘制药-时曲线,计算在不同MIC值时2组血浆亚胺培南%T>4×MIC值.结果 血浆亚胺培南标准曲线在0.5~100 mg·L-1呈良好线性关系,r=0.999 7,最小质量浓度值0.5 mg·L-1为定量下限.对照组患者血浆亚胺培南Cmax浓度高于试验组,Cmix浓度低于试验组(均P<0.01);2组AUC0-∞、t1/2 、kel、CLtot、Vd、Vd·kg-1值比较差异无统计学意义(P>0.05);在MIC值分别为0.5、1、2 mg·L-1时,试验组血浆亚胺培南%T>4×MIC值高于对照组(P<0.01);在MIC为4 mg·L-1时,2组血浆亚胺培南%T>4×MIC均<40%,但2组比较差异无统计学意义(P>0.05).结论 在治疗重症肺炎患者时,延长亚胺培南-西司他丁钠静脉输注时间可增加血浆亚胺培南谷浓度及%T>4×MIC.随着MIC升高,2组%T>4×MIC呈下降趋势.当MIC≥4 mg·L-1时,两种给药方式均不能达到良好杀菌效果,推荐增大给药剂量或者更换其他抗生素治疗.
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