Pharmacokinetics and Pharmacokinetic-Dynamic Modeling of an 8- Aminoquinoline Candidate Anticyanide Drug (WR242511)
Abstract
Cyanide is one of the most rapidly acting toxic compounds. With a sufficiently high dose one may die within minutes of exposure. Treatment must be rapid to be effective. Cyanide is used extensively in industry and agriculture in a variety of forms which may lead to inadvertent human exposure. Agents useful in treating cyanide intoxication include sodium nitrite, 4- dimethylaminophenol, cobalt EDTA, and hydroxycobalamin. Sodium nitrite and 4- dimethylaminophenol dimethylaminophenol work by converting hemoglobin to methemoglobin for which cyanide has a very high affinity thus acting as a cyanide sink. Cobalt EDTA and hydroxycobalamin act directly as cyanide chelators. Sodium thiosulfate is administered in conjunction with sodium nitrite to accelerate conversion of cyanide to thiocyanate which is nontoxic and excreted in the urine. All of the above treatments require intravenous delivery and careful monitoring by trained medical personnel. Hydrogen cyanide is considered a serious chemical warfare threat because it can be delivered to the battlefield in concentrations sufficiently to cause extensive morbidity and mortality. In military situations the administration of any of the known antidotes would be virtually impossible because of the number of casualities, the short time span in which the antidote needs to be delivered, and the limitations of MOPP. A prophylactic drug for cyanide poisoning would be the treatment of choice to avert mass casualties. The ideal drug would be effective in the majority of the population being treated, the dosing rate would be daily or less frequent, it would have minimal side effects and would not interfere with aerobic and anaerobic work necessitated in the course of military duties.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008843
Entities
People
- Jim O. Peggins
- Larry D. Brown
- Mark T. Marino
- Michael R. Urquhart
- Thomas G. Brewer
Organizations
- Walter Reed Army Institute of Research