EFFECTS OF DILTIAZEM ON THE PHARMACOKINETICS OF NIFEDIPINE

To evaluate the effect of diltiazem pretreatment (60 mg three times a day for 3 days) on pharmacokinetics and pharmacodynamic effect of nifedipine, six healthy subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. Diltiazem induced a marked increment of the area under the plasma concentration-time curve (AUC) for nifedipine by a mean of 140% and reduced the total body clearance (Cl) from 0.0043 ± 0.0019 to 0.0017 ± 0.0006 ml/min/kg (p < 0.05, mean ± SD). The biological half-life (t) of nifedipine was prolonged from 2.46 ± 0.65 to 3.21 ± 0.92 h (p < 0.05) without any changes in indocyanine green (ICG) clearance. Diltiazem did not produce significant changes of AUC, Cl, and t for the acid metabolite of nifedipine. Blood pressure (B after nifedipine administration with diltiazem pretrer ment was more decreased than that without diltiazer Both a decreased hepatic clearance and an increased bi availability of nifedipine by diltiazem probably expla the significant changes in pharmacokinetics and hem dynamics of nifedipine. A clinically important drug ± teraction may occur with nifedipine when diltiazem administered concurrently. © 1990 Raven Press, Ltd., New York.