Abstract

Objective: We aimed to investigate the relationship between voriconazole (VRCZ) trough concentrations and hepatotoxicity and to evaluate whether the recommended trough concentration is adequate in our clinical setting. Materials and methods: A retrospective study was performed to investigate the relationship between serum VRCZ concentrations and the development of hepatotoxicity at the Kindai University Nara Hospital. Patients treated with VRCZ from March 2010 to January 2018 were identified from the medical records. A total of 42 patients (mean age of 61.9 ± 16.9 years; 33 males and 9 females) were enrolled in this study. Results: Hepatotoxicity developed in 28.6% (12/42) of patients treated with VRCZ, and 91.7% (11/12) of these patients developed hepatotoxicity within 3 weeks after initiating the treatment. Significantly increased aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.001), and alanine aminotransferase (p = 0.001) levels were observed after the initiation of VRCZ therapy. In addition, significant positive correlations between AST and VRCZ trough concentrations (p = 0.017) and between ALP and VRCZ trough concentrations (p = 0.012) were observed. VRCZ trough concentration was identified as a significant independent risk factor for hepatotoxicity (adjusted odds ratio: 1.611, 95% confidence interval: 1.131 – 2.579, p = 0.006), and the cutoff serum trough concentration was calculated to be 4.2 μg/mL. Conclusion: VRCZ-induced hepatotoxicity should be noted in the early stages of therapy. A sustained VRCZ trough concentration of ~ < 4.2 μg/mL is recommended to prevent hepatotoxicity in patients with low serum albumin levels.


This study was conducted in the Department of Pharmacy, Nara Hospital, Japan.

Author Details

Authors

• Atsushi Hirata¹
• Keisuke Noto¹
• Ryosuke Ota¹
• Satoshi Yokoyama²
• Kouichi Hosomi²
• Mitsutaka Takada²
• Hiroshi Matsuoka¹

Departments

• ¹ Department of Pharmacy, Kindai University Nara Hospital, and 

• ² Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Japan

Address

Mitsutaka Takada, PhD

Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
Email: 
takada@
phar.kindai.ac.jp

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