某醫院血液科成年病人使用抗黴菌藥Voriconazole之血中波谷濃度監測暨分析C-反應蛋白對其濃度的影響

Voriconazole Trough Concentration Monitoring of Adult Patients with Hematologic Malignancies and the Impact of C-Reactive Protein on Plasma Drug Concentrations in a Single Center

鄭吉元(Chi-Yuan Cheng) ； 王博南(Po-Nan Wang) ； 郭明宗(Ming-Chung Kuo) ； 洪玉馨(Yu-Shin Hung) ； 林棟樑(Tung-Liang Lin) ； 黃雅卿(Ya-Ching Huang) ； 王元欽(Yuen-Chin Wang) ； 高小雯(Hsiao-Wen Kao) ； 張鴻(Hung Chang) ； 蔡慈貞(Tzu-Cheng Tsai)

《臺灣臨床藥學雜誌》 30卷1期 (2022/01) Pp. 48-58

https://doi.org/10.6168/FJCP.202201_30(1).0005

摘要

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。

關鍵字

Voriconazole ； 藥物血中濃度監測 ； 血中波谷濃度 ； C-反應蛋白

並列摘要

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.

並列關鍵字

Voriconazole ； Therapeutic Drug Monitoring (TDM) ； Blood Trough Concentration ； C-Reactive Protein (CRP)