Effectiveness of Fluconazole for Pulmonary Aspergilloma and Its Concentration in Lung Tissue
Fluconazole was administered to two male patients aged 41 and 70 years with pulmonary aspergilloma, the diagnosis of which was based on "fungus balls" on chest X-ray films, isolation of Aspergillus from the sputum and positive serum precipitation antibody against Aspergillus. The patients received a 100 to 200 mg oral daily dose of fluconazole for six months. The fungus balls shrank and disappeared and Aspergillus culture and the serum antibody became negative. No recurrence has been observed during the two years since the end of treatment. To determine the mechanism by which fluconazole was effective in the treatment of pulmonary aspergilloma, drug levels in the blood and normal and affected lung tissues were determined in 14 patients who received surgery for lung resection. The patients generally received a 200 mg oral daily dose of fluconazole for four days prior to the surgery, during which samples of blood and healthy and affected lung tissues were collected for the determination of fluconazole levels by HPLC. The average fluconazole concentration was 8.2 μ/ml in the blood (14 patients), 9.4 μg/g in healthy lung tissue (10 patients) and 7.7 μg/g in lung lesions (12 patients). Although the results suggested that the drug was well distributed into the blood and lung tissue when administered at an oral dose of 200 mg, the drug levels obtained were found to be far below the growth inhibitory level of fluconazole against Aspergillus. Therefore, it may be essential for the future development of antifungal agents and for a better understanding of the pharmacological action of fluconazole to evaluate the mechanism by which the drug exerts its therapeutic effect on aspergilloma at below its growth inhibitory level.