浏览全部资源
扫码关注微信
昆明市第一人民医院药学部,昆明 650224
药师,硕士研究生。研究方向:临床药学。E-mail:1983378655@qq.com
主任药师,硕士生导师。研究方向:临床药学和药物基因组学。E-mail:songcs163@163.com
收稿日期:2024-07-31,
修回日期:2024-11-30,
录用日期:2024-12-03,
纸质出版日期:2025-01-30
移动端阅览
李雅暄,李兴德,王国徽,等.基因多态性对侵袭性真菌感染患者伏立康唑血药浓度影响的Meta分析[J].中国药房,2025,36(02):225-231.
LI Yaxuan,LI Xingde,WANG Guohui,et al.Meta-analysis of the effects of gene polymorphism on plasma concentration of voriconazole in patients with invasive fungal infection[J].ZHONGGUO YAOFANG,2025,36(02):225-231.
李雅暄,李兴德,王国徽,等.基因多态性对侵袭性真菌感染患者伏立康唑血药浓度影响的Meta分析[J].中国药房,2025,36(02):225-231. DOI: 10.6039/j.issn.1001-0408.2025.02.16.
LI Yaxuan,LI Xingde,WANG Guohui,et al.Meta-analysis of the effects of gene polymorphism on plasma concentration of voriconazole in patients with invasive fungal infection[J].ZHONGGUO YAOFANG,2025,36(02):225-231. DOI: 10.6039/j.issn.1001-0408.2025.02.16.
目的
2
评价基因多态性对侵袭性真菌感染患者伏立康唑(VRZ)血药谷浓度(
c
min
)的影响。
方法
2
检索the Cochrane Library、Embase、PubMed、Web of Science、中国生物医学文献数据库、中国知网、维普网和万方数据,收集基因多态性与VRZ
c
min
相关的文献,检索时间为建库至2024年4月。筛选文献,提取资料,评价文献质量后,使用R 4.3.2软件进行Meta分析。
结果
2
共纳入21篇文献,共计2 454例患者。Meta分析结果显示,
CYP2C19
IM型、PM型患者的VRZ
c
min
均显著高于EM型,而IM型显著低于PM型(
P
<0.01);
CYP2C9
rs1057910 AA型患者的VRZ
c
min
显著高于AC/CC型,
CYP3A5
rs776746 CC型患者的VRZ
c
min
显著高于TT型(
P
<0.01);
POR
rs10954732 GG型患者的VRZ
c
min
显著高于GA型和AA型,
POR
rs1057868 CT型患
者的VRZ
c
min
显著低于TT型(
P
<0.01);
ABCB1
rs1045642
CC型患者的VRZ
c
min
显著高于TT型(
P
<0.05);
NR1I2
rs2472677 CT型患者的VRZ
c
min
显著高于TT型,
NR1I2
rs7643645 AA型患者的VRZ
c
min
显著高于AG型(
P
<0.05);
ABCC2
rs717620 CC型患者的VRZ
c
min
均显著低于CT型和TT型,且CT型显著低于TT型(
P
<0.01)。
结论
2
CYP2C19
、
CYP2C9
rs1057910、
CYP3A5
rs776746、
POR
rs10954732、
ABCB1
rs1045642、
NR1I2
rs7643645突变等位基因均可导致VRZ血药浓度降低,
ABCC2
rs717620突变等位基因则可导致VRZ血药浓度升高。
OBJECTIVE
2
To evaluate the influence of gene polymorphism on plasma minimum concentration (
c
min
) of voriconazole (VRZ) in patients with invasive fungal infection.
METHODS
2
The Cochrane Library, Embase, PubMed, Web of Science, China Biomedical Literature Database, CNKI, VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and
c
min
of VRZ from inception to April 2024. After screening the literature, extracting data, and evaluating the quality of the literature, meta-analysis was performed using R 4.3.2 software.
RESULTS
2
A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ
c
min
of
CYP2C19
IM and PM types was significantly higher than EM type, and the VRZ
c
min
of IM type was significantly lower than PM type (
P
<0.01). The VRZ
c
min
of
CYP2C9
rs1057910 AA type was significantly higher than
AC/CC type, and that of
CYP3A5
rs776746 CC type was significantly higher than TT type (
P
<0.01). The VRZ
c
min
of
POR
rs10954732 GG type was significantly higher than GA and AA types, and that of
POR
rs1057868 CT type was significantly lower than TT type (
P
<0.01). The VRZ
c
min
of
ABCB1
rs1045642 CC type was significantly higher than TT type (
P
<0.05). The VRZ
c
min
of
NR1I2
rs2472677 CT type was significantly higher than TT type, and rs7643645 AA type was significantly higher than AG type (
P
<0.05). The VRZ
c
min
of
ABCC2
rs717620 CC type was significantly lower than CT type and TT type, and the CT type was significantly lower than TT type (
P
<0.01).
CONCLUSIONS
2
Mutant alleles in
CYP2C19
,
CYP2C9
rs1057910,
CYP3A5
rs776746,
POR
rs10954732,
ABCB1
rs1045642 and
NR1I2
rs7643645 can lead to a decrease in VRZ plasma concentration,
and mutant allele in
ABCC2
rs717620 can lead to an increase in VRZ plasma concentration.
PATTERSON T F , 3rd THOMPSON G R , DENNING D W , et al . Practice guidelines for the diagnosis and management of aspergillosis:2016 update by the Infectious Diseases Society of America [J ] . Clin Infect Dis , 2016 , 63 ( 4 ): e1 - e60 .
DENNING D W , RIBAUD P , MILPIED N , et al . Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis [J ] . Clin Infect Dis , 2002 , 34 ( 5 ): 563 - 571 .
SCHULZ J , KLUWE F , MIKUS G , et al . Novel insights into the complex pharmacokinetics of voriconazole:a review of its metabolism [J ] . Drug Metab Rev , 2019 , 51 ( 3 ): 247 - 265 .
CHEN K , ZHANG X L , KE X Y , et al . Individualized medication of voriconazole:a practice guideline of the division of therapeutic drug monitoring,Chinese Pharmaco-logical Society [J ] . Ther Drug Monit , 2018 , 40 ( 6 ): 663 - 674 .
任佳秀 , 倪受东 , 李萌 , 等 . 伏立康唑的治疗药物浓度监测影响因素的研究进展 [J ] . 现代药物与临床 , 2021 , 36 ( 7 ): 1545 - 1548 .
REN J X , NI S D , LI M , et al . Research progress on influen-cing factors of voriconazole therapeutic drug concentration monitoring [J ] . Drugs Clin , 2021 , 36 ( 7 ): 1545 - 1548 .
ZHONG X F , TONG X L , JU Y , et al . Interpersonal factors in the pharmacokinetics and pharmacodynamics of voriconazole:are CYP2C19 genotypes enough for us to make a clinical decision? [J ] . Curr Drug Metab , 2018 , 19 ( 14 ): 1152 - 1158 .
GARCÍA I G , CARCAS A J , BOROBIA A M . Strategy to effectively and efficiently implement voriconazole pharmacogenetics in clinical practice [J ] . Pharmacogenomics , 2020 , 21 ( 10 ): 647 - 649 .
DOLTON M J , MIKUS G , WEISS J , et al . Understanding variability with voriconazole using a population pharmacokinetic approach:implications for optimal dosing [J ] . J Antimicrob Chemother , 2014 , 69 ( 6 ): 1633 - 1641 .
桂明珠 . 伏立康唑治疗儿童侵袭性真菌感染的血药浓度意义与潜在影响因素研究 [D ] . 上海 : 上海交通大学 , 2020 .
GUI M Z . Study on the significance and potential in-fluencing factors of plasma concentration of voriconazole in the treatment of invasive fungal infections in children [D ] . Shanghai : Shanghai Jiao Tong University , 2020 .
DERMAUW W , VAN LEEUWEN T . The ABC gene family in arthropods:comparative genomics and role in insecticide transport and resistance [J ] . Insect Biochem Mol Biol , 2014 , 45 : 89 - 110 .
LYNCH C , SAKAMURU S , HUANG R L , et al . Characterization of human pregnane Ⅹ receptor activators identified from a screening of the Tox21 compound library [J ] . Biochem Pharmacol , 2021 , 184 : 114368 .
SHIRASAKA Y , CHAUDHRY A S , MCDONALD M , et al . Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content [J ] . Pharmacogeno-mics J , 2016 , 16 ( 4 ): 375 - 387 .
袁梦莹 , 潘婷 , 何霞 , 等 . 老年共病患者使用伏立康唑时药物基因型与血药浓度的相关性分析 [J ] . 中国临床药理学杂志 , 2023 , 39 ( 8 ): 1090 - 1094 .
YUAN M Y , PAN T , HE X , et al . Analysis of the correlation between drug genotype and blood concentration in elderly patients with comorbidities using voriconazole [J ] . Chin J Clin Pharmacol , 2023 , 39 ( 8 ): 1090 - 1094 .
ZENG G T , SHI L H , LI H L , et al . Effect of cyclosporine a and polymorphisms in CYP2C19 and ABCC2 on the concentration of voriconazole in patients undergoing allogeneic hematopoietic stem cell transplantation [J ] . Xeno-biotica , 2020 , 50 ( 5 ): 614 - 619 .
AIUCHI N , NAKAGAWA J , SAKURABA H , et al . Impact of polymorphisms of pharmacokinetics-related genes and the inflammatory response on the metabolism of voriconazole [J ] . Pharmacol Res Perspect , 2022 , 10 ( 2 ): e00935 .
ZHAO T , SHEN H , ZHANG H L , et al . Association of CYP2C19,CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients [J ] . Pharmacogenomics , 2023 , 24 ( 3 ): 141 - 151 .
王霖霖 . 药物基因组学与肾功能对伏立康唑稳态谷浓度的影响研究 [D ] . 长沙 : 中南大学 , 2024 .
WANG L L . Research on impact of pharmacogenetic and renal function on the steady-state concentration of vorico-nazole [D ] . Changsha : Central South University , 2024 .
SHEN K L , GU Y , WANG Y , et al . Therapeutic drug monitoring and safety evaluation of voriconazole in the treatment of pulmonary fungal diseases [J ] . Ther Adv Drug Saf , 2022 , 13 : 20420986221127503 .
LITTLE J , HIGGINS J P , IOANNIDIS J P , et al . Streng-thening the reporting of genetic association studies(STREGA):an extension of the STROBE Statement [J ] . Hum Genet , 2009 , 125 ( 2 ): 131 - 151 .
刘鸣 . 系统评价、Meta分析设计与实施方法 [M ] . 北京 : 人民卫生出版社 , 2011 : 72 .
LIU M . Design and implementation of systematic eva-luation,meta-analysis [M ] . Beijing : People’s Medical Medical Publishing House , 2011 : 72 .
李宇 . 基于CYP2C19基因多态性检测与血药浓度监测的伏立康唑临床个体化用药研究 [D ] . 合肥 : 安徽中医药大学 , 2017 .
LI Y . Clinical individualized use of voriconazole based on CYP2C19 gene polymorphism detection and blood concentration monitoring [D ] . Hefei : Anhui University of Chinese Medicine , 2017 .
王陶陶 , 胡萨萨 , 尤海生 , 等 . 恶性血液病患者中伏立康唑血药浓度监测及其影响因素的探讨 [J ] . 中国医院药学杂志 , 2018 , 38 ( 7 ): 693 - 696,707 .
WANG T T , HU S S , YOU H S , et al . Monitoring vorico-nazole concentrations and identifying the influence factors in patients with hematological malignancy [J ] . Chin J Hosp Pharm , 2018 , 38 ( 7 ): 693 - 696,707 .
王新茗 . 伏立康唑血药浓度监测方法的建立与CYP2C19基因多态性检测的临床应用 [D ] . 成都 : 成都医学院 , 2019 .
WANG X M . Establishment of a method for monitoring the plasma concentration of voriconazole and clinical application of CYP2C19 gene polymorphism detection [D ] . Chengdu : Chengdu Medical College , 2019 .
熊芳 , 郭虎 , 陈茂林 , 等 . CYP2C19基因多态性对侵袭性真菌感染患者伏立康唑游离型药物浓度的影响 [J ] . 药物分析杂志 , 2019 , 39 ( 2 ): 291 - 295 .
XIONG F , GUO H , CHEN M L , et al . Influence of CYP2C19 gene polymorphism on unbound plasma concentrations of voriconazole in patients with invasive fungal infections [J ] . Chin J Pharm Anal , 2019 , 39 ( 2 ): 291 - 295 .
孙钰珊 . 采用伏立康唑抗真菌治疗的肝硬化患者血清伏立康唑谷浓度分布特征及影响因素 [J/OL ] . 中国肝脏病杂志 (电子版), 2018 , 10 ( 3 ): 86 - 89 [ 2024-04-30 ] . https://kns.cnki.net/kcms2/article/abstract?v=ifIT5_n5_GekUb6-mXAZGxFUMlT-49Csk9QTZzh8JawoVwNh7mgf2hsCi-0TM9TNetBf69U7-emyKgPwnMwLQQBraELaYsqOoE9e-knP-QOFIpjUzx_RYtvvI3lIldYJIi4ISRNhVwbHCrZoK1a-FpwX2-BR_Xkc0mJUowB-xVxt7_foSmN_yfzZ8DvL21_oDiA&uniplatform=NZKPT&language=CHS. DOI:10.3969/j.issn.1674-7380.2018.03.016 https://kns.cnki.net/kcms2/article/abstract?v=ifIT5_n5_GekUb6-mXAZGxFUMlT-49Csk9QTZzh8JawoVwNh7mgf2hsCi-0TM9TNetBf69U7-emyKgPwnMwLQQBraELaYsqOoE9e-knP-QOFIpjUzx_RYtvvI3lIldYJIi4ISRNhVwbHCrZoK1a-FpwX2-BR_Xkc0mJUowB-xVxt7_foSmN_yfzZ8DvL21_oDiA&uniplatform=NZKPT&language=CHS.DOI:10.3969/j.issn.1674-7380.2018.03.016 .
SUN Y S . Distribution characteristics and influencing factors of valley concentration of serum voriconazole in liver cirrhosis patients who underwent antifungal therapy with voriconazole [J/OL ] . Chin J Liver Dis Electron Version , 2018 , 10 ( 3 ): 86 - 89 [ 2024-04-30 ] . https://kns.cnki.net/kcms2/article/abstract?v=ifIT5_n5_GekUb6mXAZGxFUMlT-49Csk9QTZzh8JawoVwNh7mgf2hsCi0TM9TNetBf69U7-emyKgPwnMwLQQBraELaYsqOoE9e-knP-QOFIpjUzx_RYtvvI3lIldYJIi4ISRNhVwbHCrZoK1aFpwX2-BR_X-kc0mJUowB-xVxt7_foSmN_yfzZ8DvL21_oDiA&unipla-tform=NZKPT&language=CHS. DOI:10.3969/j.issn.1674-7380.2018.03.016 https://kns.cnki.net/kcms2/article/abstract?v=ifIT5_n5_GekUb6mXAZGxFUMlT-49Csk9QTZzh8JawoVwNh7mgf2hsCi0TM9TNetBf69U7-emyKgPwnMwLQQBraELaYsqOoE9e-knP-QOFIpjUzx_RYtvvI3lIldYJIi4ISRNhVwbHCrZoK1aFpwX2-BR_X-kc0mJUowB-xVxt7_foSmN_yfzZ8DvL21_oDiA&unipla-tform=NZKPT&language=CHS.DOI:10.3969/j.issn.1674-7380.2018.03.016 .
王百乔 , 赵震宇 , 韩敏 , 等 . 伏立康唑治疗侵袭性真菌感染致肝损伤影响因素及CYP2C19基因多态性 [J ] . 中华医院感染学杂志 , 2021 , 31 ( 13 ): 1957 - 1962 .
WANG B Q , ZHAO Z Y , HAN M , et al . Influencing factors for invasive fungal infection-induced liver injury in patients treated with voriconazole and CYP2C19 gene polymorphisms [J ] . Chin J Nosocomiology , 2021 , 31 ( 13 ): 1957 - 1962 .
李敏 , 周丽娟 , 张华 , 等 . CYP2C19基因多态性对侵袭性真菌感染患者伏立康唑用药的指导意义探讨 [J ] . 中国医院药学杂志 , 2020 , 40 ( 2 ): 156 - 160,207 .
LI M , ZHOU L J , ZHANG H , et al . The significance of CYP2C19 gene polymorphism in guiding voriconazole administration in patients with invasive fungal infection [J ] . Chin J Hosp Pharm , 2020 , 40 ( 2 ): 156 - 160,207 .
EBRAHIMPOUR S , NAMAZI S , MOHAMMADI M , et al . Impact of CYP2C19 polymorphisms on serum concentration of voriconazole in Iranian hematological patients [J ] . J Res Pharm Pract , 2017 , 6 ( 3 ): 151 - 157 .
LI Z W , PENG F H , YAN M , et al . Impact of CYP2C19 genotype and liver function on voriconazole pharmacokinetics in renal transplant recipients [J ] . Ther Drug Monit , 2017 , 39 ( 4 ): 422 - 428 .
CHEN X M , XIAO Y H , LI H P , et al . Therapeutic drug monitoring and CYP2C19 genotyping guide the application of voriconazole in children [J ] . Transl Pediatr , 2022 , 11 ( 8 ): 1311 - 1322 .
FAN X H , ZHANG H , WEN Z P , et al . Effects of CYP2C19,CYP2C9 and CYP3A4 gene polymorphisms on plasma voriconazole levels in Chinese pediatric patients [J ] . Pharmacogenet Genomics , 2022 , 32 ( 4 ): 152 - 158 .
WANG T T , ZHU H F , SUN J Y , et al . Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections [J ] . Int J Antimicrob Agents , 2014 , 44 ( 5 ): 436 - 442 .
赵婷 , 沈皓 , 张惠兰 , 等 . 新疆维吾尔族异基因造血干细胞移植高危患儿的伏立康唑血浆谷浓度的分布特征及对疗效和不良反应的影响 [J ] . 中国医院药学杂志 , 2022 , 42 ( 23 ): 2505 - 2510,2544 .
ZHAO T , SHEN H , ZHANG H L , et al . Distribution cha-racteristics of voriconazole plasma trough concentration in Xinjiang Uygur children at high risk of allogeneic hematopoietic stem cell transplantation and its effect on efficacy and adverse reactions of voriconazole [J ] . Chin J Hosp Pharm , 2022 , 42 ( 23 ): 2505 - 2510,2544 .
CHUWONGWATTANA S , JANTARAROUNGTONG T , PROMMAS S , et al . Impact of CYP2C19,CYP3A4,ABCB1,and FMO3 genotypes on plasma voriconazole in Thai patients with invasive fungal infections [J ] . Pharmacol Res Perspect , 2020 , 8 ( 6 ): e00665 .
ZENG G T , WANG L L , SHI L H , et al . Variability of voriconazole concentrations in patients with hemato-poietic stem cell transplantation and hematological malignancies:influence of loading dose,procalcitonin,and pregnane X receptor polymorphisms [J ] . Eur J Clin Pharmacol , 2020 , 76 ( 4 ): 515 - 523 .
ALLEGRA S , FATIGUSO G , FRANCIA S , et al . Pharmacogenetic of voriconazole antifungal agent in pediatric patients [J ] . Pharmacogenomics , 2018 , 19 ( 11 ): 913 - 925 .
ZHANG Y , HOU K L , LIU F , et al . The influence of CYP2C19 polymorphisms on voriconazole trough concentrations:systematic review and meta-analysis [J ] . Mycoses , 2021 , 64 ( 8 ): 860 - 873 .
GUYOT C , HOFSTETTER L , STIEGER B . Differential effects of membrane cholesterol content on the transport activity of multidrug resistance-associated protein 2(ABCC2)and of the bile salt export pump(ABCB11) [J ] . Mol Pharmacol , 2014 , 85 ( 6 ): 909 - 920 .
0
浏览量
72
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构