TY - JOUR T1 - Effect of Calcium Channel Antagonists Nifedipine and Nicardipine on Rat Cytochrome P-450 2B and 3A Forms JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1436 LP - 1441 VL - 290 IS - 3 AU - Richard C. Zangar AU - Janice Rice Okita AU - Hyesook Kim AU - Paul E. Thomas AU - Alan Anderson AU - Robert J. Edwards AU - David L. Springer AU - Richard T. Okita Y1 - 1999/09/01 UR - http://jpet.aspetjournals.org/content/290/3/1436.abstract N2 - Calcium channel antagonists are widely prescribed for treatment of hypertension. 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 blot analyses were undertaken using antibodies specific for one or several members of these cytochrome P-450 subfamilies. Nicardipine was found to be an effective inducer of CYP3A; in particular, CYP3A23 was increased ∼36-fold following treatment with 100 mg of nicardipine/kg/day. Nicardipine induced CYP2B forms up to ∼3.1-fold. Nifedipine did not alter CYP3A expression but did increase CYP2B expression such that total CYP2B, CYP2B1, and CYP2B2v (a splice variant of CYP2B2) were increased ∼5- to 15-fold after treatment with 100 mg of nifedipine/kg/day, with increases in benzyloxyresorufin O-dealkylase and erythromycinN-demethylase activities, respectively. The distinct differences in cytochrome P-450 induction profile induced by nicardipine and nifedipine suggest that they may enhance cytochrome P-450 expression by different mechanisms unrelated to their effects on calcium channels. The American Society for Pharmacology and Experimental Therapeutics ER -