INHIBITORY EFFECTS OF PROPOFOL ON CYTOCHROME-P450 ACTIVITIES IN RAT HEPATIC MICROSOMES

The effects of propofol on cytochrome P450 activity in rat hepatic mic rosomes were evaluated to determine the potential influence of this an esthetic on the metabolism of coadministered agents. In microsomes fro m untreated and isoniazid-treated rats, propofol was a weak inhibitor of enflurane metabolism, inhibiting activity only at 0.35 mM propofol. In contrast, toluene, a related compound, effectively impaired enflur ane defluorination in microsomes from untreated, and isoniazid- and ph enobarbital-treated rats at concentrations as low as 0.025 mM. Propofo l, in contrast to toluene, was an effective inhibitor of benzphetamine demethylation where it inhibited this activity at propofol concentrat ions as low as 0.025 mM in microsomes from phenobarbital-treated rats. In microsomes from phenobarbital-treated rats, propofol potently inhi bited the metabolism of aniline. Sixty-four percent inhibition was ach ieved at 0.03 mM propofol, whereas toluene had no effect at 1 mM. Thes e data demonstrate that propofol does not effectively inhibit enfluran e metabolism performed by the isoniazid-inducible cytochrome P450IIE1 but effectively impairs activities of the phenobarbital-inducible cyto chrome P450 isozymes.