Okuda Toshikatsu, Okuda Akiko, Watanabe Noriko, Takao Masayoshi, Takayanagi Kazunobu
Department of Pharmacy, Kurashiki Central Hospital, Kurashiki City, Japan.
Yakugaku Zasshi. 2008 Dec;128(12):1811-8. doi: 10.1248/yakushi.128.1811.
We investigated the optimal blood concentration of voriconazole (VRCZ) based on trough blood concentrations (C) and serological test values in patients. With regard to the regulation of VRCZ dosage (D) to maintain optimal blood concentrations, we investigated the relationship between C and D. Twenty-three patients were enrolled in the present study, and at 28 point data were analyzed retrospectively.When the beta-D-glucan or the Aspergillus antigen were decreased below the standard set values, it was evaluated as effective. The adverse events were evaluated using the Common Terminology Criteria for Adverse Events ver. 3.0. We found a significant difference (p<0.05) in the average trough blood concentration between patients in whom VRCZ was effective and those in whom VRCZ was ineffective (8.21+/-2.19 microg/ml vs. 1.01+/-0.86 microg/ml), and patients presenting with adverse events and those with no adverse events (7.64+/-2.84 microg/ml vs. 1.49+/-1.79 microg/ml). There was no significant relationship between C and D (C: D, y=0.018-2.186, r(2)=0.349).Improved efficacy and more adverse events thus occurred with higher blood concentrations. The careful regulation of the dosage must be performed while measuring blood concentration and observing for adverse events. The implementation of therapeutic drug monitoring for VRCZ is a valuable tool for achieving effective fungal infection therapy and should be aggressively investigated in future studies.
我们根据患者的血药谷浓度(C)和血清学检测值,研究了伏立康唑(VRCZ)的最佳血药浓度。关于调整VRCZ剂量(D)以维持最佳血药浓度,我们研究了C与D之间的关系。本研究共纳入23例患者,并对28个时间点的数据进行回顾性分析。当β-D-葡聚糖或曲霉抗原降至设定标准值以下时,判定为治疗有效。使用不良事件通用术语标准第3.0版评估不良事件。我们发现VRCZ治疗有效的患者与无效的患者之间的平均血药谷浓度存在显著差异(p<0.05)(8.21±2.19μg/ml对1.01±0.86μg/ml),出现不良事件的患者与未出现不良事件的患者之间也存在显著差异(7.64±2.84μg/ml对1.49±1.79μg/ml)。C与D之间无显著相关性(C:D,y=0.018 - 2.186,r²=0.349)。因此,血药浓度越高,疗效改善但不良事件增多。在测量血药浓度并观察不良事件时,必须谨慎调整剂量。实施VRCZ治疗药物监测是实现有效真菌感染治疗的一项有价值的工具,应在未来研究中积极探索。