Imipenem/cilastatin: evolution of the sustained-release intramuscular formulation

Related Experiment Video

Updated: Aug 15, 2026

A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
09:17

A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii

Published on: January 2, 2017

F M Kahan1, J D Rogers

  • 1Merck Sharp & Dohme Research Laboratories, Rahway, N.J.

Chemotherapy
|January 1, 1991
PubMed

Insights

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.

More Related Videos

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials06:18

A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials

Published on: March 3, 2023

Related Concept Videos

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence01:22

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions01:24

Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
Modified-Release Drug Delivery Systems: Rate-Programmed II01:19

Modified-Release Drug Delivery Systems: Rate-Programmed II

Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
Modified-Release Drug Delivery Systems: Rate-Programmed I01:22

Modified-Release Drug Delivery Systems: Rate-Programmed I

Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
Production of Antibiotics01:27

Production of Antibiotics

Penicillin, one of the earliest and most widely used antibiotics, is produced industrially by the filamentous fungus Penicillium chrysogenum. Large stirred-tank bioreactors ranging from tens to hundreds of thousands of liters maintain tightly controlled temperature, pH, and dissolved oxygen conditions to support fungal metabolism and maximize antibiotic yield. Penicillin is a secondary metabolite, synthesized primarily during the stationary growth phase, which requires a carefully managed...
Production of Pharmaceuticals01:30

Production of Pharmaceuticals

Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...