- 作者：Yosuke Suzuki ; Issei Tokimatsu ; Yuhki Sato ; Kanako Kawasaki ; Yukie Sato ; Tomomi Goto ; Kazuhiko Hashinaga ; Hiroki Itoh ; Kazufumi Hiramatsu ; Jun-ichi Kadota
- 关键词：Voriconazole ; Therapeutic drug monitoring ; TDM ; Hepatotoxicity ; Trough ; Pharmacokinetics
- 刊名：Clinica Chimica Acta
- 出版年：2013
- 出版时间：23 September, 2013
- 年：2013
- 卷：424
- 期：Complete
- 页码：119-122
- 全文大小：227 K
Background
Therapeutic drug monitoring (TDM) of voriconazole is important to optimize efficacy and to minimize toxicity and intolerance. In this study, we evaluated the effect of sustained high plasma trough concentration of voriconazole on the incidence of hepatotoxicity in hospitalized Japanese patients.Methods
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).
Results
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.
Conclusions
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.