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Pharmacology

Pharmacokinetics of Meropenem in Critically Ill Patients with Acute Renal Failure Treated by Continuous Hemodiafiltration

W. A. Krueger, T. H. Schroeder, M. Hutchison, E. Hoffmann, H.-J. Dieterich, A. Heininger, C. Erley, A. Wehrle, K. Unertl
W. A. Krueger
Department of Anesthesiology and
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T. H. Schroeder
Department of Anesthesiology and
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M. Hutchison
ZENECA Pharmaceuticals, Mereside, Alderly Park, Macclesfield, Cheshire, United Kingdom
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E. Hoffmann
Department of Anesthesiology and
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H.-J. Dieterich
Department of Anesthesiology and
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A. Heininger
Department of Anesthesiology and
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C. Erley
Department of Internal Medicine, Tübingen University Hospital, Tübingen, Germany, and
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A. Wehrle
Department of Anesthesiology and
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K. Unertl
Department of Anesthesiology and
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DOI: 10.1128/AAC.42.9.2421
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    Fig. 1.

    Levels of meropenem in plasma (means and standard deviations) in eight anuric critically ill patients treated by continuous hemodiafiltration. A dose of 1,000 mg of meropenem was administered as an i.v. infusion over 30 min.

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    Demographic and diagnostic information and pharmacokinetic parameters following administration of 1,000 mg of meropenem i.v. for nine anuric critically ill patients treated by continuous hemodiafiltrationa

    Patient no.SexbAge (yr)Weight (kg)DiagnosisInfection (APACHE-II scores)cDiafiltrate (liters/h)t1/2αd (t1/2β) (h)AUC0–12 (μg · h/ml)CLtotal (CLCVVHDF) (ml/min)Vssd (liters/kg of body wt)
    1eF3965Mitral valve endocarditis, respiratory failure, progressive liver failure, pelvic venous thrombosisEndocarditis, brain abscess  (34, 21)1,8500.15  (7.38)287.557.98  (31.5)0.32
    2M6566Thoracoabdominal aortic aneurysm, aortic valve regurgitation, hemorrhage, compartment syndrome of left lower limbPneumonia  (28, 20)1,7250.21  (3.92)343.148.59  (30.0)0.27
    3eF6866Low output syndrome after bivalvular replacement, pulmonary edemaSepsisf  (15, 14)1,8750.16  (4.51)295.456.43  (33.4)0.28
    4eM7576Coronary bypass, hemorrhage, respiratory failurePneumoniaf  (36, 24)1,6500.12  (4.75)354.347.05  (29.2)0.25
    5gF1965Polytrauma, subdural hematomaPneumonia, sepsis  (37, 24)
    6M6691Myocardial infarctions, mitral valve regurgitation, coronary bypass, postoperative ventricular fibrillation, thrombopeniaPneumoniaf  (28, 22)1,7250.02  (4.82)539.230.92  (30.2)0.08
    7F3056Cardiomyopathy, respiratory failure, thyreotoxicosisPneumonia  (14, 20)1,6250.21  (2.80)480.934.66  (27.5)0.17
    8M6570Thoracic aortic aneurysm, hematothorax, respiratory failureSepsisf  (26, 34)1,8500.12  (4.54)250.166.65  (32.5)0.30
    9M6170Cardiopulmonary resuscitation, aortic valve replacement, recurrent ventricular fibrillationPneumonia  (39, 22)1,6250.17  (3.50)201.682.69  (28.9)0.38
    Mean54.269.4 (28.6, 22.3)1,7410.15  (4.53)344.053.12  (30.4)0.26
    SD19.79.7 (9.1, 5.3)1050.06  (1.35)114.416.83  (2.0)0.09
    • ↵a t1/2α, distribution half-life; t1/2β, elimination half-life; AUC0–12, area under the concentration-time curve of plasma meropenem concentrations; CLtotal, total body clearance of meropenem; CLCVVHDF, clearance of meropenem by continuous venovenous hemodiafiltration;Vss, apparent volume of distribution at steady state.

    • ↵b F, female; M, male.

    • ↵c APACHE-II scores were determined within 24 h of admission to the intensive-care unit and on the day of the pharmacokinetic investigation.

    • ↵d Values derived from fitted biexponential model.

    • ↵e Patient died in intensive-care unit.

    • ↵f Clinical diagnosis could not be proven by microbiological culture.

    • ↵g Patient recovered from renal failure; no pharmacokinetic analysis was done.

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Pharmacokinetics of Meropenem in Critically Ill Patients with Acute Renal Failure Treated by Continuous Hemodiafiltration
W. A. Krueger, T. H. Schroeder, M. Hutchison, E. Hoffmann, H.-J. Dieterich, A. Heininger, C. Erley, A. Wehrle, K. Unertl
Antimicrobial Agents and Chemotherapy Sep 1998, 42 (9) 2421-2424; DOI: 10.1128/AAC.42.9.2421

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Pharmacokinetics of Meropenem in Critically Ill Patients with Acute Renal Failure Treated by Continuous Hemodiafiltration
W. A. Krueger, T. H. Schroeder, M. Hutchison, E. Hoffmann, H.-J. Dieterich, A. Heininger, C. Erley, A. Wehrle, K. Unertl
Antimicrobial Agents and Chemotherapy Sep 1998, 42 (9) 2421-2424; DOI: 10.1128/AAC.42.9.2421
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KEYWORDS

acute kidney injury
hemodiafiltration
Thienamycins

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