The Formation of Cytochrome P-450-Metabolic Intermediate Complexes from Amines, in the Isolated Perfused Rat Liver

Abstract

1. Cytochrome P-450-metabolic intermediate (MI) complexes were formed from SKF 525-A, propoxyphene, acetylmethadol, noracetylmethadol, norbenzphetamine, and N-hydroxyamphetamine, but not methadone, in the isolated perfused rat liver.

2. The amount of MI complex from SKF 525-A (8% of the cytochrome P-450) after 1 h exceeded that for all other compounds (1-2%).

3. Both MI complex and residual substrate contributed to the inhibition of mixed-function oxidase activity observed. No substrate altered the total cytochrome P-450 concentration or NADPH-cytochrome c reductase activity.

4. The formation of MI complexes in isolated perfused liver corresponds to that seen m whole animals, and contrasts with that seen in microsomal preparations.