The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine

Eur J Clin Pharmacol. 1999 Mar;55(1):57-60. doi: 10.1007/s002280050593.


Objective: The primary aim of the present study was to investigate the effect of ketoconazole on the pharmacokinetics of nisoldipine.

Methods: A single dose of nisoldipine 5 mg immediate-release tablet was administered either alone or in combination with ketoconazole 200 mg (4 days pretreatment and concomitant administration) in a randomized crossover trial in seven healthy male Caucasian volunteers. Plasma concentration-versus-time profiles of nisoldipine and its metabolite M9 were determined.

Results: Pre-treatment with and concomitant administration of ketoconazole resulted in a 24-fold and 11-fold, increase in mean AUC and Cmax of nisoldipine, respectively, compared with treatment with nisoldipine 5 mg alone. The ketoconazole-induced increase in plasma concentration of the metabolite M9 was of similar magnitude.

Conclusion: The interaction is attributed to inhibition of cytochrome 3A4-mediated first-pass metabolism. Ketoconazole and other antifungal drugs of the substituted imidazole type as well as other potent inhibitors of cytochrome 3A4 should not be used concomitantly with nisoldipine.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antifungal Agents / chemistry*
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Cross-Over Studies
  • Drug Interactions
  • Humans
  • Ketoconazole / pharmacology*
  • Male
  • Nisoldipine / adverse effects
  • Nisoldipine / pharmacokinetics*
  • Nisoldipine / pharmacology
  • Time Factors


  • Antifungal Agents
  • Calcium Channel Blockers
  • Nisoldipine
  • Ketoconazole