Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy
Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy
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DOI：
10.1007/s00134-008-1034-7
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发表时间：
2008-06-01
影响因子：
38.9
通讯作者：
Kees, Frieder
中科院分区：
文献类型：
--
作者：
Langgartner, Julia;Vasold, Antje;Kees, Frieder
目的：β-内酰胺类抗生素的临床效果取决于药物浓度高于敏感细菌的最小抑菌浓度（MIC）的时间。因此，持续输注（CI）β-内酰胺类药物（如美罗培南）可能是比间歇性推注（IB）更合理的方法。本研究的目的是检验美罗培南CI在接受连续性肾脏替代治疗（CRRT）的患者中是否达到与IB相当的有效药物浓度。设计：前瞻性、随机交叉研究。单位：双床重症监护病房（ICU）。患者和干预措施：6例ICU患者随机接受美罗培南1 g IB每12 h一次或0.5 g i. v.负荷剂量，随后24 h内2 g i. v. CI。2天后，方案交叉。在第2天和第4天测定美罗培南的药代动力学。测量和结果：短期输注1 g美罗培南后的血清峰浓度[中位数（25%和75%四分位数）]为62.8（51.4; 85.0）mg/l，12 h时的谷浓度为8.1（4.5; 18.7）mg/l，血清半衰期为5.3（5.1; 7.0）h。CI期间的稳态浓度为18.6（13.3; 24.5）mg/l。两种治疗期间的AUC相当，分别测定为233（202; 254）mg/l*h（IB）和227（182; 283）mg/l*h（CI）。IB后4小时，药物浓度降至CI稳态浓度以下。结论：CRRT患者中美罗培南的适当抗菌浓度很容易通过CI达到。CI可能是IB的有效替代给药方案。有必要对两种给药方案的临床疗效进行前瞻性比较。
Objective: The clinical effect of beta-lactam antibiotics depends on the time of drug concentration above the minimal inhibitory concentration ( MIC) for a susceptible bacterium. Continuous infusion ( CI) of ss-lactams such as meropenem may therefore be a more rational approach than intermittent bolus injections ( IB). The aim of this study was to test whether CI of meropenem achieves effective drug concentrations comparable to IB in patients treated by continuous renal replacement therapy ( CRRT). Design: Prospective, randomised cross-over study. Setting: Twelve-bed medical intensive care unit ( ICU). Patients and interventions: Six ICU patients were randomised to receive either meropenem 1 g IB every 12 h or a 0.5 g i.v. loading dose followed by 2g i.v. CI over 24h. After 2 days, regimens were crossed over. Meropenem pharmacokinetics were determined on days 2 and 4. Measurements and results: Peak serum concentration [ median ( 25% and 75% quartiles)] after short infusion of 1 g meropenem were 62.8 ( 51.4; 85.0) mg/l, trough levels at 12 h were 8.1 (4.5; 18.7) mg/l, and serum half-life was 5.3 (5.1; 7.0) h. Steady-state concentrations during CI were 18.6 (13.3; 24.5) mg/l. The AUCs during either treatment were comparable and determined as 233 ( 202; 254) mg/l*h ( IB) and 227 ( 182; 283) mg/l*h ( CI), respectively. Four hours after IB, drug concentrations dropped below CI steady-state concentrations. Conclusion: Appropriate antibacterial concentrations of meropenem in patients with CRRT are easily achievable with CI. CI may be an effective alternative dosing regimen to IB. A prospective comparison of the clinical efficacy of the two dosage regimens is warranted.