Meropenem clinical pharmacokinetics

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.
• 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.