The clinical pharmacokinetics of itraconazole: an overview

Mycoses. 1989:32 Suppl 1:67-87. doi: 10.1111/j.1439-0507.1989.tb02296.x.

Abstract

Itraconazole (R 51211) is the prototype of a class of triazole antifungals characterized by a high lipophilicity. This property determines to a large extent the pharmacokinetics of itraconazole and differentiates it from the hydrophilic triazole antifungal fluconazole. The pharmacokinetics of itraconazole in man are characterized by a good oral absorption, an extensive tissue distribution with tissue concentrations many times higher than in plasma, a relatively long elimination half-life of about one day and a biotransformation into a large number of metabolites. One of them, hydroxy-itraconazole, is antifungally active and explains why antifungal plasma levels, when measured by bioassay, are about three times the itraconazole levels measured by a specific HPLC-method. Distribution studies have shown that therapeutically active levels of itraconazole are maintained much longer in some infected tissues than in plasma. For instance, active levels persist for four days in the vaginal epithelium after a one-day treatment and for 3 weeks in the stratum corneum of the skin after treatment has been stopped. Unlike fluconazole, itraconazole does not interfere with mammalian drug metabolizing enzymes, minimizing the risk of interaction with concomitantly administered drugs. These pharmacokinetic properties may contribute to the high efficacy and safety of itraconazole in patients with various mycotic infections. New pharmaceutical formulations are being explored in order to broaden the application field of itraconazole to intravenous and oral therapy of patients with malabsorption.

Publication types

  • Review

MeSH terms

  • Absorption
  • Antifungal Agents / pharmacokinetics*
  • Half-Life
  • Humans
  • Itraconazole
  • Ketoconazole / analogs & derivatives*
  • Ketoconazole / pharmacokinetics
  • Tissue Distribution

Substances

  • Antifungal Agents
  • Itraconazole
  • Ketoconazole