Pharmacokinetics of meropenem in intensive care unit patients receiving continuous veno-venous hemofiltration or hemodiafiltration
作者:
Lucy Giles,
Anne Jennings,
Alison Thomson,
Gary Creed,
Richard Beale,
Angela McLuckie,
期刊:
Critical Care Medicine
(OVID Available online 2000)
卷期:
Volume 28,
issue 3
页码: 632-637
ISSN:0090-3493
年代: 2000
出版商: OVID
关键词: meropenen;carbapenems;lactams;pharmacokinetics;half-life;hemofiltration;hemodiafiltration;renal replacement therapy;acute renal failure;critical care
数据来源: OVID
摘要:
Objective:To evaluate an intravenous meropenem dosage regimen in adult intensive care patients with acute renal failure treated by continuous renal replacement therapy.Design:A prospective, clinical study.Setting:General intensive care unit of a university hospital.Patients:Ten critically ill adult patients being treated with meropenem and receiving continuous veno-venous hemofiltration (hemofiltration rates, 1-2 L/hr) (n = 5) or continuous veno-venous hemodiafiltration (hemofiltration rates, 1-1.5 L/hr; dialysis rates, 1-1.5 L/hr) (n = 5) via a polyacrylonitrile hollow fiber 0.9-m2filter.Interventions:Patients received a meropenem dose of 1 g iv every 12 hrs as a 5-min bolus.Measurements and Main Results:Meropenem concentrations were measured by high-performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration-time profiles, derive pharmacokinetic variable estimates, and determine sieving coefficients and filter clearances. The serum concentrations were examined to see whether they were above the minimum inhibitory concentrations (MICs) for pathogens that may be encountered in intensive care patients. Serum concentrations exceeded 4 mg/L (MIC90forPseudomonas aeruginosa) during 67% of the dosage period in all patients. Sub-MIC90concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after treatment. Mean (SD) (n = 10) pharmacokinetic variable estimates were as follows: elimination half-life, 5.16 hrs (1.83 hrs); volume of distribution, 0.35 L/kg (0.10 L/kg); and total clearance, 4.30 L/hr (1.38 L/hr). A sieving coefficient of 0.93 (0.06) (n = 9) indicated free flow across the filter. The fraction cleared by the extracorporeal route was 48% (13%) (n = 9), which is clinically important.Conclusions:A meropenem dose of 1 g iv every 12 hrs provides adequate serum concentrations in the majority of patients receiving continuous veno-venous hemofiltration or continuous veno-venous hemofiltration with a 0.9-m2polyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of up to 3 L/hr. A lower dose would not be sufficient for the empirical treatment of potentially life-threatening infections in all patients.
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