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The pharmacology of meropenem, a new carbapenem antibiotic
1Infectious Diseases Section, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705-2286, USA.
Abstract:
Meropenem, a new carbapenem antibiotic, is more active against gram-negative bacilli and less active against gram-positive cocci than is imipenem, and there are several important structural differences between meropenem and the older carbapenem. These differences may be responsible for the lower potential for the induction of epileptogenic activity observed with meropenem as well as for its increased stability to degradation by dehydropeptidase-I. The pharmacokinetics of meropenem are typical of those of a parenteral beta-lactam antibiotic with low protein binding and predominantly renal excretion. Dosage reduction is required in patients with reduced renal function; no dosage adjustment is required for patients with hepatic impairment. Meropenem has excellent penetration in abdominal tissues, bile, blister fluid, inflammatory exudate, cerebrospinal fluid (in the presence of inflammation), gynecologic tissues, respiratory tract tissues, and urinary tract tissues; tissue levels are generally equal to or above the levels needed for the treatment of patients with susceptible pathogens.
Insights
Meropenem offers improved activity against gram-negative bacteria and enhanced stability compared to imipenem. This new carbapenem antibiotic demonstrates favorable pharmacokinetic properties and excellent tissue penetration for treating infections.
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Meropenem is a novel carbapenem antibiotic.
- It exhibits distinct structural differences from imipenem.
- These differences influence its antimicrobial spectrum and stability.
Purpose of the Study:
- To compare the activity and properties of meropenem with imipenem.
- To evaluate the pharmacokinetic profile of meropenem.
- To assess meropenem's tissue penetration.
Main Methods:
- Comparative analysis of antimicrobial activity.
- Pharmacokinetic studies in parenteral administration.
- Assessment of tissue distribution and penetration.
Main Results:
- Meropenem shows greater activity against gram-negative bacilli and less activity against gram-positive cocci than imipenem.
- Meropenem has a lower potential for inducing epileptogenic activity and increased stability against dehydropeptidase-I.
- Pharmacokinetics are typical for parenteral beta-lactams, with low protein binding and renal excretion.
- Excellent tissue penetration observed in various sites, including CSF, abdominal tissues, and respiratory tract.
Conclusions:
- Meropenem presents an advantageous profile compared to imipenem, particularly for gram-negative infections.
- Its pharmacokinetic properties and tissue penetration support its efficacy in treating susceptible pathogens.
- Dosage adjustments are necessary for renal impairment, but not hepatic impairment.