[Correlations between drug plasma concentration and adverse effects in patients treated with itraconazole for pulmonary aspergilloma]

We measured the plasma concentration of itraconazole (ITCZ) in 18 patients who received ITCZ for the treatment of pulmonary aspergilloma. Abnormal laboratory values were observed in 4 out of 10 patients who received 200 mg/day, 1 out of 3 patients who received 300 mg/day, and 2 out of 5 patients who received 400 mg/day. Four patients discontinued ITCZ therapy because of adverse effects following the administration of 200 mg/day or 400 mg/day. The mean plasma ITCZ concentration was 622 ng/ml in patients treated with less than 4 mg/kg, and 1,352 ng/ml in patients treated with more than 4 mg/kg of ITCZ. The sensitivity of Aspergillus species to ITCZ was measured with the NCCLS microdilution method, using alamar blue indicator. The MIC50 of ITCZ was 0.5 microg/ ml for 25 strains of A. fumigatus, 4 microg/ml for 15 strains of A. niger, and 0.25 microg/ml for 10 strains of A. flavus. In conclusion, this study underscored the necessity of monitoring the plasma concentration of ITCZ for effective treatment of patients with pulmonary aspergilloma.