Effect of nifedipine on the enzyme-inducing activity of phenobarbital and beta-naphthoflavone

Studies were made of the effect of nifedipine on the enzyme-inducing activity of phenobarbital and beta-naphthoflavone estimated by hexobarbital sleeping time, benzphetamine-N-demethylase (BND), ethoxycumarin-O-deethylase (ECOD) and ethoxyresorufin-O-deethylase. (EROD) activity, as well as by the cytochrome P-450 and cytochrome b5 content. Nifedipine at the dose used (100 mg/kg, orally) prolonged hexobarbital sleeping time and affected neither the BND, ECOD and EROD activity, nor the cytochrome P-450 and cytochrome b5 content. On single application nifedipine exerted a different effect on the phenobarbital- or beta-naphthoflavone-provoked enzyme induction. The phenobarbital-induced BND activity and the cytochrome P-450 content were not changed, while the beta-naphthoflavone-induced EROD activity and cytochrome P-450 and cytochrome b5 content decreased, the ECOD activity remaining unchanged. Nifedipine administered for three days significantly increased the BND activity and the cytochrome P-450 content. The three-day administration of nifedipine plus phenobarbital resulted in a further increase in the BND activity and the cytochrome P-450 content. Consistent with this finding was the potentiation of the phenobarbital-induced shortening of hexobarbital sleep. Nifedipine administered at a single dose, one hour before beta-naphthoflavone had no effect per se but potentiated the enzyme-inducing effect of beta-naphthoflavone on the EROD activity and the cytochrome P-450 content but not on the ECOD activity. These data could be taken into account when considering the possible interactions between nifedipine and other drugs applied at different sequence and duration.