Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects

Br J Clin Pharmacol. 2001 May;51(5):443-50. doi: 10.1046/j.1365-2125.2001.01372.x.


Aims: Itraconazole is a potent inhibitor of CYP3A4 activity and is often used in combination with corticosteroids. Since the latter are partly metabolized by CYP3A4, we studied the interaction between itraconazole, prednisone and methylprednisolone in healthy male subjects.

Methods: The effects of 4 days administration of oral itraconazole (400 mg on the first day then 200 mg day-1 for 3 days) on the pharmacokinetics of prednisolone after a single oral dose of prednisone (60 mg) and the pharmacokinetics of methylprednisolone after single oral dose of methylprednisolone (48 mg) were studied in 14 healthy male subjects in a two-period cross-over trial. Plasma cortisol concentrations were determined as a pharmacodynamic index.

Results: Itraconazole increased the mean area under the methylprednisolone concentration-time curve from 2773 ng ml-1 h to 7011 ng ml-1 h (P < 0.001) and the elimination half-life from 3.2 h to 5.5 h (P < 0.001). The pharmacokinetics of prednisolone were unchanged. Cortisol concentrations at 24 h were lower after administration of methylprednisolone with itraconazole than after methylprednisolone alone (24 ng ml-1 vs 109 ng ml-1, P < 0.001).

Conclusions: Itraconazole increased methylprednisolone concentrations markedly with enhanced suppression of endogenous cortisol secretion, but had no effect on prednisolone pharmacokinetics. The pharmacokinetic interaction between methylprednisolone and itraconazole is probably related to inhibition of hepatic CYP3A4 activity by itraconazole.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antifungal Agents / pharmacology
  • Bodily Secretions / drug effects
  • Cross-Over Studies
  • Drug Interactions
  • Glucocorticoids / pharmacokinetics
  • Humans
  • Hydrocortisone / metabolism*
  • Itraconazole / analogs & derivatives*
  • Itraconazole / pharmacology*
  • Male
  • Methylprednisolone / pharmacokinetics*
  • Prednisolone / pharmacokinetics*


  • Antifungal Agents
  • Glucocorticoids
  • hydroxyitraconazole
  • Itraconazole
  • Prednisolone
  • Hydrocortisone
  • Methylprednisolone