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

Abstract

1. 1. The effects of three calcium antagonists (CA), nifedipine (NF), verapamil (V) and diltiazem (DL) on the enzyme-inducing activity of phenobarbital (PB) and β-naphthoflavone (β-NF) were measured by hexobarbital (HB) sleeping time, benzphetamine-N-demethylase (BND) ethoxycourmarin-O-deethylase (ECOD) and ethoxyresorufin-O-deethylase (EROD) activities, as well as by the cytochrome P-450 and cytochrome b5 content. 2. 2. NF, V and DL at oral doses of 100, 80 and 60 mg/kg administered 1 hr before PB additionally shortened the HB sleeping time. 3. 3. Single administration of calcium antagonists on the background of developed PB-provoked enzyme induction prolonged the PB-shortened hexobarbital sleeping time. 4. 4. Three day administration of NF, V and DL plus PB slightly decreased the enzyme-inducing effect of PB on BND activity and cytochrome P-450 and cytochrome b5 content. 5. 5. NF and V administered only once after PB-provoked enzyme induction increased the PB enzyme-inducing effect on BND activity and on the content of cytochrome P-450. DL decreased the PB-induced BND activity and cytochrome P-450 and cytochrome b5 content. 6. 6. The calcium antagonists studied affected the enzyme-inducing activity of β-NF to a lesser extent when compared to PB. Only NF was found to potentiate the enzyme-inducing effect of β-NF on the EROD activity and on the cytochrome P-450 content.