Delayed decrease in voriconazole concentration after resolution of inflammation in a patient with invasive pulmonary aspergillosis: a case report

BACKGROUND: Voriconazole (VRCZ) is an effective treatment for pulmonary aspergillosis. Active infectious disease leads to a reduction in cytochrome P450 activity, resulting in increased VRCZ concentrations. However, the impact of VRCZ dose reduction during the severe inflammatory state on VRCZ concentrations after the resolution of inflammation is not yet fully understood. Here, we report the time-course changes in VRCZ blood concentrations after inflammation in a patient with invasive pulmonary aspergillosis. CASE PRESENTATION: A man in his 60s receiving oral VRCZ tablets at 400 mg/day for invasive pulmonary aspergillosis developed marked inflammation due to bacterial pneumonia and influenza virus infection. C-reactive protein (CRP) levels increased to a peak of 35.54 mg/dL, with a concomitant elevation in the VRCZ trough concentration to 4.7 µg/mL. Following dose reduction to VRCZ 300 mg/day, the trough concentration decreased to 1.1 µg/mL on day 11 after dose reduction, while CRP declined to 4.78 mg/dL after antibiotic therapy. VRCZ was continued at the same dose. However, four weeks after CRP levels had stabilized, the VRCZ concentration decreased to 0.6 µg/mL. After re-escalation of VRCZ to 400 mg/day, the trough concentration returned to the effective therapeutic range of 1.1 µg/mL. CONCLUSIONS: After infection is controlled, VRCZ concentrations may decrease to levels below the therapeutic range. Following VRCZ dose reduction during a high inflammatory state, reassessment of trough concentrations after improvement of inflammation may be useful to prevent excessive decreases in VRCZ concentrations.