Delayed decrease in voriconazole concentration after resolution of inflammation in a patient with invasive pulmonary...

Area of Science:

• Pharmacology
• Infectious Diseases
• Critical Care Medicine

Background:

• Voriconazole (VRCZ) is a key antifungal for pulmonary aspergillosis.
• Active infections can elevate VRCZ levels by reducing cytochrome P450 activity.
• The effect of VRCZ dose reduction during inflammation on post-inflammation levels is unclear.

Purpose of the Study:

• To investigate the time-course changes in VRCZ blood concentrations after inflammation resolution.
• To assess the impact of VRCZ dose reduction during severe inflammation on subsequent VRCZ levels.

Main Methods:

• Case report of a patient with invasive pulmonary aspergillosis and severe inflammation.
• Monitoring of VRCZ trough concentrations and C-reactive protein (CRP) levels.
• Analysis of VRCZ levels following dose reduction during inflammation and after CRP stabilization.

Main Results:

• High CRP (35.54 mg/dL) correlated with elevated VRCZ (4.7 µg/mL).
• Dose reduction to 300 mg/day led to decreased VRCZ (1.1 µg/mL) as CRP improved (4.78 mg/dL).
• Post-inflammation, VRCZ levels dropped to 0.6 µg/mL, necessitating a dose increase to 400 mg/day to reach 1.1 µg/mL.

Conclusions:

• VRCZ concentrations can fall below therapeutic levels after infection control.
• Reassessing VRCZ trough levels post-inflammation is crucial after dose reduction during acute illness.
• This reassessment helps prevent subtherapeutic drug concentrations and ensures effective treatment.