Page 92 - 《中国药房》2023年4期

成人患者体内伏立康唑代谢的影响因素分析
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程 林 ，梁再明，喻明洁，孙凤军，戴 青（陆军军医大学第一附属医院药学部，重庆 400038）
中图分类号 R969.1；R969.3 文献标志码 A 文章编号 1001-0408（2023）04-0466-05
DOI 10.6039/j.issn.1001-0408.2023.04.16

摘 要 目的 分析影响成人患者体内伏立康唑代谢的因素，为伏立康唑的临床合理应用提供参考。方法 回顾性分析2021年4
月－2022年3月我院使用伏立康唑并进行治疗药物监测的103例成人患者资料，同时测定血浆伏立康唑谷浓度（c0 ）、伏立康唑氮
氧化物浓度（cN ），并计算c0/cN值；采用Pearson’s相关性分析影响伏立康唑c0、c0/cN值的因素；采用多元线性回归模型分析伏立康唑
c0、c0/cN值的独立影响因素。结果 患者基础疾病以肺炎、肾脏疾病和白血病为主；感染真菌中以曲霉菌、念珠菌和酵母样真菌为
主；给药方式主要为静脉滴注，以联用质子泵抑制剂患者最多。C反应蛋白（CRP）、总胆红素（TBIL）、直接胆红素（DBIL）、间接胆
红素（IBIL）水平与伏立康唑c0均呈正相关，血小板计数和白蛋白水平与伏立康唑c0均呈负相关；CRP、TBIL、DBIL水平与c0/cN值均
呈正相关，白蛋白水平与c0/cN值呈负相关。多元线性回归模型分析结果显示，伏立康唑c0的独立影响因素有CRP、IBIL、伏立康唑
给药方式和给药剂量，伏立康唑c0/cN的独立影响因素有CRP、DBIL和年龄。结论 CRP、IBIL、伏立康唑给药方式和给药剂量是影
响伏立康唑c0的独立因素，CRP、DBIL和年龄是影响c0/cN值的独立因素；临床使用伏立康唑时，应考虑上述指标对伏立康唑代谢的
影响，合理调整伏立康唑的给药方式和剂量。
关键词 伏立康唑；伏立康唑氮氧化物；治疗药物监测；谷浓度；影响因素；相关性

Analysis of influencing factors for the metabolism of voriconazole in adult patients
CHENG Lin，LIANG Zaiming，YU Mingjie，SUN Fengjun，DAI Qing（Dept. of Pharmacy， the First Affiliated
Hospital of Army Medical University， Chongqing 400038， China）

ABSTRACT OBJECTIVE To analyze the influencing factors for the metabolism of voriconazole in adult patients， and to
provide reference for the rational use of voriconazole in clinic. METHODS The clinical data of adult patients admitted in our
hospital receiving voriconazole and therapeutic drug monitoring from April 2021 to March 2022 were collected. The trough
concentration of voriconazole （c0 ） and plasma concentration of voriconazole-N-oxide concentration （cN ） were determined， and
voriconazole-to-voriconazole N-oxide concentration ratio （c0/cN ） was calculated. Pearson’s correlation analysis was used to analyze
the influencing factors for c0 and c0/cN of voriconazole. Multiple linear regression models were used to analyze the independent
influencing factors for c0 and c0/cN of voriconazole. RESULTS The underlying diseases of the patients were mainly pneumonia，
kidney disease and leukemia. The detected fungi were mainly Aspergillus， Candida and yeast-like fungi. Voriconazole was mainly
administered by intravenous drip， especially in patients who used proton pump inhibitor in combination. The levels of C-reactive
protein （CRP）， total bilirubin （TBIL）， direct bilirubin （DBIL） and indirect bilirubin （IBIL） were positively correlated with c0 of
voriconazole， while platelet count and albumin levels were negatively correlated with voriconazole c0. The levels of CRP， TBIL and
DBIL were positively correlated with c0/cN， while albumin levels were negatively correlated with c0/cN. Multiple linear regression
analysis showed that the independent influencing factors of voriconazole c0 included the levels of CRP and IBIL， route of
administration and dose of voriconazole， and the independent influencing factors of voriconazole c0/cN were the levels of CRP and
DBIL and age. CONCLUSIONS The levels of CRP and IBIL， route of administration and dose of voriconazole are independent
influencing factors of voriconazole c0； the levels of CRP and DBIL and age are independent influencing factors of voriconazole c0/cN.
The influence of above indexes on the metabolism of voriconazole should be considered when using voriconazole clinically； and the
route of administration and dose of voriconazole should be adjusted reasonably.
KEYWORDS voriconazole； voriconazole-N-oxide； therapeutic drug monitoring； trough concentration； influencing factor；
correlation

伏立康唑属于第二代三唑类广谱抗真菌药，临床除 用于免疫抑制患者（如血液恶性肿瘤患者和器官移植患
[1]
可广泛用于侵袭性曲霉菌和念珠菌感染的治疗外，还可 者）真菌感染的预防 。伏立康唑主要在肝脏由细胞色
素 P450 酶（cytochrome P450 enzyme，CYP）中 的
Δ 基金项目 重庆市科卫联合医学科研项目（No.2021MSXM218）
CYP2C19、CYP3A4和CYP2C9代谢，由于该药的代谢呈
＊第一作者 副主任药师，硕士。研究方向：抗感染药物的治疗药 [2―4]
物监测。电话：023-68766797。E-mail：cheng7zhu@163.com 非线性药动学特征，故其血药浓度个体差异大 。有
# 通信作者 副主任药师。研究方向：药物分析。电话：023- 研究显示，伏立康唑治疗窗窄，中国人群伏立康唑的有
[5]
68766797。E-mail：dq050@163.com 效治疗浓度为 0.5～5.0 μg/mL 。伏立康唑的疗效和不

· 466 · China Pharmacy 2023 Vol. 34 No. 4 中国药房 2023年第34卷第4期