Imipenem/cilastatin: evolution of the sustained-release intramuscular formulation
1Merck Sharp & Dohme Research Laboratories, Rahway, N.J.
Chemotherapy
|January 1, 1991
Summary
A new intramuscular formulation of imipenem/cilastatin maintains effective drug levels longer than IV doses. This sustained release offers a promising new option for treating serious polymicrobial and multiresistant infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Drug Delivery Systems
Background:
- Imipenem/cilastatin is an established monotherapy for complex infections.
- Current administration is typically intravenous, requiring multiple infusions.
- A novel sustained-release intramuscular formulation has been developed.
Purpose of the Study:
- To evaluate the pharmacokinetic profile and potential efficacy of a new intramuscular imipenem/cilastatin formulation.
- To compare the duration of effective plasma concentrations with intramuscular versus intravenous administration.
Main Methods:
- Pharmacokinetic studies in animal models and healthy human volunteers.
- Analysis of plasma imipenem concentrations over time.
- Comparison of sustained levels against established susceptibility breakpoints and minimum inhibitory concentrations.
Main Results:
- The intramuscular formulation significantly prolonged the duration of plasma imipenem concentrations above susceptibility breakpoints compared to intravenous doses.
- While peak concentrations were lower, the sustained release achieved longer periods above minimum inhibitory concentrations.
- Animal and human studies demonstrated favorable pharmacokinetic profiles.
Conclusions:
- The sustained-release intramuscular formulation of imipenem/cilastatin sodium demonstrates potential for effective treatment of infections.
- This formulation may offer an advantageous alternative to intravenous administration, particularly for infections of mild to moderate severity.
- Sustained drug exposure, rather than peak concentration, appears critical for beta-lactam efficacy.
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