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Meropenem clinical pharmacokinetics

J W Mouton1, J N van den Anker

  • 1Department of Clinical Microbiology, Erasmus University, Rotterdam, The Netherlands.

Clinical Pharmacokinetics
|April 1, 1995
PubMed
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Meropenem, a carbapenem antibiotic, offers broad-spectrum activity and improved stability over imipenem. Its pharmacokinetic profile and renal excretion allow for dose adjustments based on creatinine clearance in patients with renal insufficiency.

Area of Science:

  • Pharmacology
  • Microbiology
  • Drug Metabolism

Background:

  • Meropenem is a carbapenem antibiotic with broad-spectrum activity against Gram-positive and Gram-negative bacteria.
  • It is more stable to dehydropeptidase I (DHP-I) hydrolysis than imipenem, eliminating the need for coadministration with a DHP-I inhibitor like cilastatin.
  • Meropenem may exhibit reduced nephrotoxicity and neurotoxicity compared to imipenem.

Purpose of the Study:

  • To characterize the pharmacokinetic properties of meropenem.
  • To investigate the elimination pathways and half-life of meropenem.
  • To establish the basis for dosage adjustments in patients with renal impairment.

Main Methods:

  • Intravenous administration of meropenem in healthy volunteers.

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  • Measurement of plasma meropenem concentrations over time.
  • Analysis of urinary excretion of meropenem and its metabolites.
  • Correlation of elimination half-life with creatinine clearance.

    • Main Results:

    • Peak plasma concentration (Cmax) of approximately 30 mg/L after a 1g IV dose.
    • Elimination half-life (t1/2) of approximately 1 hour.
    • Linear dose-related increase in the area under the plasma concentration-time curve.
    • Predominantly extracellular distribution with a volume of distribution of 21L.
    • Elimination via metabolism and excretion, with up to 70% recovered in urine as unchanged drug or a metabolite (ICI 213689).
    • Prolonged half-life in renal insufficiency, correlating with creatinine clearance.

    Conclusions:

    • Meropenem demonstrates favorable pharmacokinetics and a wide spectrum of activity.
    • Its stability to DHP-I and potential for reduced toxicity offer advantages over imipenem.
    • Dosage adjustments for meropenem in renal insufficiency can be guided by creatinine clearance measurements.