Marked intra- and inter-patient variability of itraconazole steady state plasma concentrations

Therapie. 1996 Mar-Apr;51(2):163-7.

Abstract

Itraconazole is a new oral triazole antifungal agent that is effective against a wide range of fungal pathogens, including Aspergillus species. There has been a considerable increase in recent years in its use in prophylaxis of aspergillosis in neutropenic patients. A total of 74 trough concentrations of itraconazole+active metabolite were retrospectively analysed at steady state in 16 patients admitted to hospital for acute myeloid leukaemia (12) or malignant lymphoma (4). The minimum therapeutic concentration (itraconazole+hydroxyitraconazole = 1000 ng/ml) was never reached in 31 per cent of patients (5/16) and a constant efficient plasma concentration was obtained in only 19 per cent (3/16) with a daily regimen of 400-600 mg. The plasma levels of patients at the same daily dose differed up to 15-fold. This study confirms the pronounced inter-patient variability of unchanged itraconazole concentrations previously found in volunteers and patients. The plasma levels in six patients during successive chemotherapy treatments also varied greatly. Intra-individual differences were more accurately examined in six patients given 600 mg itraconazole/day during their first chemotherapy treatment. The trough plasma concentrations on day 15 and day 25 varied from -53 to +245 per cent. These results indicate that the plasma itraconazole concentration of neutropenic patients must be monitored to ensure that each individual is given a clinically effective dose.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use
  • Aspergillosis / prevention & control
  • Follow-Up Studies
  • Humans
  • Individuality
  • Itraconazole / administration & dosage
  • Itraconazole / blood*
  • Itraconazole / therapeutic use
  • Middle Aged
  • Neutropenia / complications
  • Time Factors

Substances

  • Antifungal Agents
  • Itraconazole