title: Therapeutic drug monitoring of voriconazole in Japanese patients: analysis based on clinical practice data.
abstract: The aim of this study was to investigate whether routine therapeutic drug monitoring (TDM) of voriconazole (VRCZ) reduced discontinuation due to hepatotoxicity. Hepatotoxicity was observed in 15 (51.7%) out of 29 patients. The percentages of patients who developed hepatotoxicity within 4 days and 1 week were 26.7 and 46.7%, respectively. The drug trough concentrations in patients with and without hepatotoxicity were 5.55 ± 2.73 and 2.36 ± 1.67 μg/ml (P < 0.01, the two-sided Student's t-test), respectively. Trough concentrations reached the target of 1-5 μg/ml in patients with gradual dose reductions based on TDM, and, consequently, liver enzyme levels returned to the original levels before the VRCZ treatment. All patients eventually continued effective VRCZ therapy despite its hepatotoxicity. Thus, dose adjustments by TDM to achieve the target trough concentrations is useful in order to avoid hepatotoxicity and enable continued effective VRCZ therapy for Japanese patients with invasive fungal infections.
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Abematsu
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Shigemi
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanazawa
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Watanabe
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan.|b Department of Clinical Pharmacotherapy , Hiroshima University , Hiroshima , Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: b Department of Clinical Pharmacotherapy , Hiroshima University , Hiroshima , Japan.
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.affiliation: b Department of Clinical Pharmacotherapy , Hiroshima University , Hiroshima , Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D044466:Asian People; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D065819:Voriconazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole
keywords: Hepatotoxicity; Japanese; Therapeutic drug monitoring; Voriconazole