Serum concentrations of itraconazole were monitored as part of a clinical trial of prophylaxis in neutropenic patients receiving treatment for haematological malignancies. Patients in the itraconazole arm received 5.0 mg/kg itraconazole (as an oral solution, Sporonax liquid), in divided doses (2.5 mg/kg b.d.). Blood samples were taken at weekly intervals immediately before the morning dose of itraconazole to establish trough drug concentrations. Serum was separated and analysed by high-performance liquid chromatography with a detection limit of 10 Âµ/L and coefficients of variation of 2.2-7.8 over the concentration range 20-1600 Âµg/l. Assays were performed at two laboratories using identical methods. Clinical results have been published separately and a full, pharmacokinetic evaluation is underway, but interim results from 145 patients who received itraconazole and provided at least one blood sample during their first prophylaxis episode are available. Mean serum itraconazole concentrations were 532 ng/ml (Â±SD 61) after one week's treatment, 673 ng/ml (Â±419) after two weeks, 1014 mg/ml (Â±739) after three weeks and 1299 ng/ml (Â±861) after four weeks. Earlier studies suggest that protection against Aspergillus infections in particular is greater at serum levels greater than 250 ng/ml. Of those patients providing blood samples, 73% had concentrations >250 ng/ml at week 1, 82% at week 2, 86% at week 3 and 92% at week 4. We conclude that the absorption of itraconazole oral solution in neutropenic patients receiving chemotherapy is reliable and therefore routine monitoring is not required.
Full conference title:
39th meeting of the American Society for Haemotology
- ASH 39th (1998)