The Myotoxic Effects of Microencapsulated Naproxen and Carrier Polymer After Intramuscular Injection in Rats
Abstract
At the present time ketorolac is the only NSAID approved for intravenous and intramuscular use in humans. The half-life of naproxen is 12-15 hours compared to 4-6 hours for ketoralac, and naproxen has an antipyretic effect. A drug carrier system has been developed which allows for highly lipophilic compounds such as naproxen to be microencapsulated (MEC) for parenteral use. Intramuscular MEC naproxen could provide greater pain relief than ketoralac with a longer duration of action. MEC naproxen could also be given to reduce or replace opioid analgesics and reduce hyperthermia in patients unable to receive oral or rectal antipyretics. Since an assessment of the potential for local toxicity of a product intended for intramuscular injection is an important component of an initial drug development strategy, this research was conducted to determine the potential for myotoxicity from intramuscular MEC naproxen. Forty female Sprague Dawley rats were given intramuscular injections of 150 mg/kg MEC naproxen into the right gastrocnemius muscle with an equal volume of carrier polymer alone injected into the left. Animals were placed into four groups often for sacrifice at 24 hours, 72 hours, one week, and one month post-injection. Multiple tissue sections were cut, stainedwith hematoxylin and eosin, and examined under light microscopy for histopathologic changes. All samples were blinded before grading by a pathologist using the following scoring system: 0 = no damage; 1 = sparsely scattered hyalinized fibers and a localized inflammatory reaction; 2 = definite fiber destruction with the presence of macrophage digestion of muscle fibers and a mixed cellular infiltrate in some but not all sections examined; 3 = widespread muscle damage throughout the original specimen.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 10, 1996
- Accession Number
- AD1011503
Entities
People
- Kevin J. Bohan
Organizations
- Uniformed Services University of the Health Sciences