Median Lethal Dose Determination of Subcutaneous Carfentanil in Ferrets
Abstract
Carfentanil is an opioid that is 10,000 times more potent than morphine and 100 times more potent than fentanyl. It produces analgesia, incapacitation, respiratory depression, and death at various doses, but its toxicity has been elaborated only to a limited extent using various laboratory animal models. Because one likely route of carfentanil exposure is inhalation, we sought to elaborate carfentanil toxicity in ferrets to fill a key gap in the research data and set the stage for subsequent studies using other routes of exposure (such as inhalation). The pulmonary structure and function of ferrets resembles that of humans, making the ferret an excellent animal model for investigating inhaled toxicants. The current study exposed water-regulated and unregulated male ferrets to carfentanil via subcutaneous injection, which provides a controlled method of exposure that is also safe and easily achieved. Initial toxic signs were lethargy and ataxia, which progressed tofasciculation and unconsciousness at moderate doses. At higher doses, respiratory distress and death were comorbid with occasional convulsions. The median lethal dose was estimated to be 27.77 micro g/kg, and water regulation status did not alter carfentanil toxicity. These data help to elaborate carfentanil toxicity in an animal model that offers advantages for studies of inhaled toxicants, and provide a relevant foundation for ongoing and planned studies of inhalation and intravenous carfentanil exposure and medical treatment of opioid overdose.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 18, 2018
- Accession Number
- AD1061244
Entities
People
- Mark C. Moffett
- Nathaniel C. Rice
- Todd M. Myers
Organizations
- United States Army Medical Research Institute of Chemical Defense