目的：

Voriconazole 的療效具有相當大的個體差異性，我國對其血中波谷濃度(trough concentration, [Vori]T) 監測的研究發表文獻甚少。有鑑於此，本研究將進行本院血液科成年病人 [Vori]T 的監測及視其濃度值和臨床反應予以介入。此外，由於國外文獻指出血中C- 反應蛋白 (C-reactive protein, CRP) 和 [Vori]T 兩者具有正相關，因此本研究也會分析CRP 對 [Vori]T 的影響。

 

方法：

本研究乃前瞻性觀察及介入研究，納入2019 年3 月至2021 年2 月期間，18歲（含）以上血液科住院病人使用抗黴菌藥voriconazole 者，在使用voriconazole 3 ~ 5天後測 [Vori]T，每位個案最多採血6 次。血漿中voriconazole 濃度的檢測方式是採用液相層析質譜／質譜儀 (liquid chromatography tandem mass spectrometry, LC-MS/MS)。另外，在每次測 [Vori]T 當天抽血測CRP。研究期間也檢視其併用藥物及監測voriconazole副作用。

 

結果：

總共取得有效樣本20 位病人之48 筆（ 人次） 抽血資料。首次投予voriconazole 其 [Vori]T 範圍可從0.2 ~ 9.6 mg/L，差距達48 倍。[Vori]T > 5.5 mg/L 組的平均CRP 高達197 mg/L，遠大於 [Vori]T ≤ 5.5 mg/L 組的平均CRP 52 mg/L。有11人次（9 位）發生voriconazole 副作用，占所有個案的45% 及占所有人次的23%，多為輕度第一級肝炎，而對於 [Vori]T > 5.5 mg/L 者則有55% 的副作用發生率。

 

結論：

本研究顯示， 血液科成年病人依照建議劑量投予voriconazole 後，其voriconazole 血中濃度個體差異性大。[Vori]T > 5.5 mg/L 者， 一半以上會產生voriconazole 副作用。CRP會影響 [Vori]T，尤其當CRP > 200 mg/L 時會顯著增加 [Vori]T。

 

 

Objective: 

Voriconazole metabolism exhibits high inter-individual variations. There are few published data on voriconazole trough concentration ([Vori]T) monitoring in Taiwan. Therefore, we conducted a [Vori]T monitoring study at our hospital. We also analyzed the effect of C-reactive protein (CRP) on [Vori]T.

 

Methods: 

Patients older than 18 years with hematological malignancies were prospectively enrolled from March 2019 to February 2021. Blood samples were collected for laboratory assays of [Vori]T. A maximum of 6 blood samples were allowed for each patient. [Vori]T was detected through liquid chromatography tandem mass spectrometry (LC-MS/MS). In addition, CRP was measured on the day of the [Vori]T test. Concomitant drug use and side effects of voriconazole during the period of this study were also examined.

 

Results: 

A total of 48 samples were obtained from 20 patients. [Vori]T ranged from 0.2 to 9.6 mg/L, a 48-fold difference. The average CRP level of the [Vori]T > 5.5 mg/L group was 197 mg/L, which was much higher than that (52 mg/L) of the [Vori]T ≤ 5.5 mg/L group. Side effects of voriconazole were observed 11 person-times (9 total patients). The most common side effect was mild hepatitis, which was indicated in 23% of samples. In the [Vori]T > 5.5 mg/L group, 55% of patients developed voriconazole-associated side effects.

 

Conclusions: 

This study discovered high variation in [Vori]T among adults with hematological malignancies. More than half of the [Vori]T > 5.5 mg/L group developed voriconazole-associated side effects. Blood CRP level may affect [Vori]T because significantly higher [Vori]T was observed in patients with a CRP level > 200 mg/L.

 

 

Summited for publication: 2021.4.5; Accepted for publication: 2021.9.14