Oral pharmacodynamic bioavailability of six p-aminophenone derivatives

Technical Report · Thu May 13 04:00:00 EDT 1993

OSTI ID:7113590

Brown, L D; Brewer, T G; Flanagan, D R; Von Bredow, J D; Brueckner, R P

A number of potential biochemical approaches exist protection against and treatment of cyanide poisoning. The methemoglobin protective approach appears to be the most promising and practical. Adequate protection against the lethal effects of cyanide intoxication depends upon a sufficient amount of available methemoglobin to bind and remove the toxic cyanide ion from the circulation. The intravenous administration of solutions of direct and indirect methemoglobin formers WR000302 (p-aminopropiophenone, PAPP), WR269,410 (p-aminoheptanophenone, PAHP), WR258,948 (p-aminooctanophenone, PAOP) and their respective N-hydroxy derivatives (WR270,1011 WR272,677 and WR271,159) to unanesthetized beagle dogs leads to a rapid increase in whole blood methemoglobin. In the absence of a specific analytical method for the accurate analysis of each of these six compounds, the corresponding whole blood methemoglobin induced by each of these compounds were monitored by the Radiometer OSM-3 hemoximeter immediately following blood sampling to construct a pharmacodynamic profile of methemoglobin vs time. When these same animals were given oral gavage doses of either a solution or suspension of the same propiophenone derivative, a rapid and consistent increase in methemoglobin levels was also observed which may be used as a measure of the rate and extent of absorption of the compound into the whole blood circulation.

• Research Organization: Walter Reed Army Inst. of Research, Washington, DC (United States). Div. of Experimental Therapeutics
• OSTI ID: 7113590
• Report Number(s): AD-P-008842/7/XAB
• Country of Publication: United States
• Language: English

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