Rosiglitazone has no clinically significant effect on nifedipine pharmacokinetics

J Clin Pharmacol. 1999 Nov;39(11):1189-94.


To examine the effects of repeat oral dosing of rosiglitazone on the pharmacokinetics of nifedipine, a prototype CYP3A4 substrate, a randomized, open-label, crossover study was performed with two treatment phases separated by a washout period of at least 14 days. Twenty-eight healthy male volunteers received either a single 20 mg oral nifedipine dose or rosiglitazone 8 mg orally once daily for 14 days with a single 20 mg oral nifedipine dose administered on day 14. Plasma nifedipine concentrations were determined over the 24-hour period following administration of the nifedipine doses. Lack of effect was defined as the demonstration that the 90% CI was contained entirely within a symmetrical 30% range either side of unity on the loge-scale. Following rosiglitazone + nifedipine administration, the area under the nifedipine concentration-time curve from time zero to infinity (AUC(0-infinity)) was 13% lower than that after administration of nifedipine alone. This difference in nifedipine AUC(0-infinity) was not deemed to be clinically significant since the 90% CI was contained within the protocol-defined 30% range (point estimate for ratio of geometric means 0.87; 90% CI: 0.79, 0.96). Rosiglitazone had no marked effect on nifedipine peak plasma concentration (point estimate: 0.99; 90% CI: 0.73, 1.34) or time to peak concentration compared with nifedipine alone. Rosiglitazone coadministration produced a small decrease in the mean nifedipine half-life (point estimate: -0.77; 90% CI: mean difference -1.29 h, -0.25 h). Both treatment regimens were well tolerated and associated with a favorable safety profile. Rosiglitazone, at the highest dose used in clinical studies, produced a small, clinically insignificant decrease in nifedipine exposure. The very small effect on nifedipine pharmacokinetics suggests that rosiglitazone is an extremely weak inducer of CYP3A4, a characteristic that distinguishes rosiglitazone from troglitazone.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / blood
  • Calcium Channel Blockers / pharmacokinetics*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Nifedipine / adverse effects
  • Nifedipine / blood
  • Nifedipine / pharmacokinetics*
  • Rosiglitazone
  • Thiazoles / administration & dosage
  • Thiazoles / adverse effects
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Time Factors


  • Calcium Channel Blockers
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Thiazoles
  • Thiazolidinediones
  • Rosiglitazone
  • Nifedipine