TY - JOUR T1 - Enhanced rates of cytochrome P450 metabolic-intermediate complex formation from nonmacrolide amines in rifampicin-treated rabbit liver microsomes. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1379 LP - 1382 VL - 23 IS - 12 AU - M R Franklin Y1 - 1995/12/01 UR - http://dmd.aspetjournals.org/content/23/12/1379.abstract N2 - The formation of cytochrome P450 metabolic-intermediate (MI) complexes from amine-containing drugs unrelated to macrolide antibiotics was investigated in hepatic microsomes from rifampicin-induced rabbits. Rifampicin treatment doubled the amount of total cytochrome P450 present. As evidenced by increased rates of erythromycin N-demethylation and MI complex formation from troleandomycin without increases in other isozyme selective oxidation reactions, the increase was predominately in the cytochrome P4503A subfamily. Fluoxetine, benzylamphetamine, propoxyphene, and norpropoxyphene formed MI complexes at rates similar to that for troleandomycin. Rates for 1-alpha-acetylmethadol and SKF 525A were 2- to 3-fold higher, and rates for the secondary amine derivatives of these two compounds, nor-1-alpha-acetylmethadol and SKF 8742A, were approximately 5-fold higher than with troleandomycin. For the SKF and acetylmethadol compounds, the rates were much higher in rifampicin-induced microsomes, compared with phenobarbital-induced microsomes. MI complex formation from benzylamphetamine was the reverse. The rate of MI complex formation from benzylamphetamine in phenobarbital-induced microsomes was similar to that from SKF 8742A and nor-1-alpha-acetylmethadol in microsomes from rabbits treated with the highest dose of rifampicin. Cytochrome P450 MI complex formation from all compounds was either low or absent from microsomes of vehicle-treated animals. ER -