The pharmacokinetics of meropenem

Area of Science:

• Pharmacology
• Microbiology
• Drug Development

Background:

• Meropenem is a novel carbapenem antibiotic.
• It possesses a 1-beta-methyl substitution for enhanced stability against human renal dehydropeptidase-I.
• An altered 2' side chain improves anti-pseudomonal activity.

Purpose of the Study:

• To characterize the pharmacokinetic and disposition profile of meropenem.
• To assess the impact of renal and hepatic functional impairment on meropenem clearance.
• To evaluate meropenem's potential as a therapeutic agent for nosocomial infections.

Main Methods:

• Pharmacokinetic studies were conducted over a dose range of 250 mg to 2 g.
• Plasma concentrations and clearance were measured.
• Urinary excretion of meropenem and its metabolite was quantified over 12 hours.
• The effect of renal and hepatic impairment on drug disposition was assessed.

Main Results:

• Meropenem exhibits linear pharmacokinetics with a terminal half-life of approximately 1 hour.
• Renal clearance is the primary route, accounting for about 70% of plasma clearance.
• Approximately 70% of the dose is recovered as intact meropenem in urine over 12 hours.
• Renal impairment predictably alters clearance; hepatic impairment does not affect disposition.

Conclusions:

• Meropenem demonstrates favorable pharmacokinetic properties and stability, similar to imipenem/cilastatin but without requiring a dehydropeptidase-I inhibitor.
• Its excellent in vitro activity and predictable disposition suggest significant potential for treating serious nosocomial infections.
• Further clinical evaluation in critically ill patients is warranted.