title: The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany.
authors: R
authors: R
authors: Heinig
authors: H G
authors: HG
authors: Adelmann
authors: G
authors: G
authors: Ahr
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000737:chemistry*; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology*; D008297:Male; D015737:Nisoldipine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D002121:Calcium Channel Blockers; D015737:Nisoldipine; D007654:Ketoconazole