Effects of diltiazem on the pharmacokinetics of nifedipine

J Cardiovasc Pharmacol. 1990 Jan;15(1):96-101. doi: 10.1097/00005344-199001000-00015.


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 less than 0.05, mean +/- SD). The biological half-life (t1/2) of nifedipine was prolonged from 2.46 +/- 0.65 to 3.21 +/- 0.92 h (p less than 0.05) without any changes in indocyanine green (ICG) clearance. Diltiazem did not produce significant changes of AUC, Cl, and t1/2 for the acid metabolite of nifedipine. Blood pressure (BP) after nifedipine administration with diltiazem pretreatment was more decreased than that without diltiazem. Both a decreased hepatic clearance and an increased bio-availability of nifedipine by diltiazem probably explain the significant changes in pharmacokinetics and hemodynamics of nifedipine. A clinically important drug interaction may occur with nifedipine when diltiazem is administered concurrently.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Diltiazem / pharmacology*
  • Drug Interactions
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Indocyanine Green
  • Kinetics
  • Male
  • Nifedipine / pharmacokinetics*
  • Nifedipine / pharmacology


  • Diltiazem
  • Nifedipine
  • Indocyanine Green