Effect of calcium channel antagonists nifedipine and nicardipine on rat cytochrome P-4502B and 3A forms

Calcium channel antagonists am widely prescribed for treatment of hypertens ion. In this study, we examined whether treatment with the calcium channel antagonists, nicardipine, nifedipine or diltiazem, alters cytochrome P-450 2B or 3A (CYP2B or CYP3A, respectively) expression in rat liver. Western bl ot analyses were undertaken using antibodies specific for one or several me mbers of these cytochrome P-450 subfamilies. Nicardipine was found to be an effective inducer of CYP3A; in particular, CYP3A23 was increased similar t o 36-fold following treatment with 100 mg of nicardipine/kg/day. Nicardipin e induced CYP2B forms up to similar to 3.1-fold. Nifedipine did not alter C YP3A expression but did increase CYP2B expression such that total CYP2B, CY P2B1, and CYP2B2v (a splice variant of CYP2B2) were increased similar to 5- to 15-fold after treatment with 100 mg of nifedipine/kg/day, with increase s in benzyloxyresorufin O-dealkylase and erythromycin N-demethylase activit ies, respectively. The distinct differences in cytochrome P-450 induction p rofile induced by nicardipine and nifedipine suggest that they may enhance cytochrome P-450 expression by different mechanisms unrelated to their effe cts on calcium channels.