Marked intra- and inter-patient variability of itraconazole steady state plasma concentrations.
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.
Poirier
J M
JM
Department of Pharmacology, Saint-Antoine Hospital, Paris, France.
Berlioz
F
F
Isnard
F
F
Cheymol
G
G
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001228:Aspergillosis / Q000517:prevention & control; D005500:Follow-Up Studies; D006801:Humans; D007206:Individuality; D017964:Itraconazole / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications; D013997:Time Factors
D000935:Antifungal Agents; D017964:Itraconazole