When l-propoxyphene-N-oxide was given orally to dogs, reduction occurred in vivo resulting in substantial plasma levels of l-propoxyphene. 2. When l-propoxyphene-N-oxide was given intravenously, near peak plasma levels of propoxyphene occurred in 10 minutes. This suggests that reduction is occurring at least in part in mammalian tissue rather than in gut flora. 3. Levopropoxyphene oxide was also readily reduced anaerobically in a rat liver microsomal fraction. 4. Results from this study explain our early observation that while l-propoxyphene-N-oxide is demethylated in vivo, demethylation does not occur in vitro when the oxide is incubated in air with liver homogenate. Thus demethylation of the oxide can occur only after reduction of the oxide to the tertiary amine. While reduction occurs readily in vivo it is completely inhibited by oxygen present in the usual microsomal incubation. 5. These studies further confirm that the N-oxide is not an intermediate in the demethylation of propoxyphene.
