Accession Number : ADP008852

Title :   Solubility and Solution Stability of WR-272677, an Oral Anticyanide Candidate

Corporate Author : SRI INTERNATIONAL MENLO PARK CA

Personal Author(s) : Pick, John ; Olson, Lori L. ; Lim, Peter ; Ellis, William Y.

Report Date : 13 MAY 1993

Pagination or Media Count : 7

Abstract : WR-272677, p-hydroxylaminoheptanophenone, has protected mice against cyanide challenge at the Battelle Laboratory. Single dose oral and intravenous pharmacokinetic and pharmacodynamic studies performed in the Division of Experimental Therapeutics at the Water Reed Army Institute of Research have shown this compound to be a potent former of methemoglobin, or ferrihemoglobin, which selectively binds cyanide. One of the steps in the development of this anticyanide agent is to determine its solubility and solution stability. The apparent room-temperature solubilities of WR-272677AB in aqueous media, ethanol, polyethylene glycol (PEG) 400, and aqueous ethanol have been determined. WR-272677AB is insoluble (<O.l mg/mL) in the aqueous media and aqueous alcohol, but is freely soluble (-400 mg/mL) in either ethanol or PEG 400. WR-272677AB dissolved in ethanol or PEG 400 under ordinary atmospheric conditions rapidly decomposes, mainly to p-azoxyheptanophenone. In the absence of molecular oxygen, however, ethanol solutions of WR-272677AB are stable for at least 24 hours.

Descriptors :   *CYANIDES, *PHARMACOKINETICS, *DRUGS, *PREVENTION, *POISONING, ALCOHOLS, ETHANOLS, GLYCOLS, MEDIA, METHEMOGLOBIN, MICE, OXYGEN, POLYETHYLENE, ROOM TEMPERATURE, SOLUBILITY, STABILITY, THERMAL PROPERTIES.

Subject Categories : Pharmacology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE