Thirty-nine patients were divided into 3 groups according to trough concentrations in two consecutive TDMs: < 4 ¦Ìg/ml in the first TDM (group A, n = 25), > 4 ¦Ìg/ml in the first and < 4 ¦Ìg/ml in the second TDM (group B, n = 8), and > 4 ¦Ìg/ml in both first and second TDMs (group C, n = 6).
Incidences of hepatotoxicity in groups A, B and C were 16.0, 25.0 and 83.3 % , and significant differences were observed between groups A and C and groups B and C. Multiple logistic regression analysis identified the classification into groups A, B and C as an independent variable of hepatotoxicity.
These results suggest that sustained high trough concentration of voriconazole may increase the risk of hepatotoxicity, and decreasing trough concentration to < 4 ¦Ìg/ml by dose adjustment after the initial TDM may reduce the incidence of hepatotoxicity in patients treated with voriconazole.