Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy.

Author(s): Langgartner J, Vasold A, Gluck T, Reng M, Kees F

Affiliation(s): Department of Internal Medicine I, University of Regensburg, 93042, Regensburg, Germany, julia.langgartner@klinik.uni-regensburg.de.

Publication date & source: 2008-02-23, Intensive Care Med., [Epub ahead of print]

Publication type:

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[Symbol: see text]g IB every 12[Symbol: see text]h or a 0.5[Symbol: see text]g i.v. loading dose followed by 2[Symbol: see text]g i.v. CI over 24[Symbol: see text]h. 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[Symbol: see text]g meropenem were 62.8 (51.4; 85.0) mg/l, trough levels at 12[Symbol: see text]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.