Effects of cytochrome P450 3A4 and non-genetic factors on initial voriconazole serum trough concentrations in hematological patients with different cytochrome P450 2C19 genotypes

被引：20

作者：

Shao, Beibei ^{[1
]}

Ma, Yongcheng ^{[1
]}

Li, Qiaoyan ^{[1
]}

Wang, Yimeng ^{[1
]}

Zhu, Zunmin ^{[2
]}

Zhao, Hongwei ^{[1
]}

Sun, Jun ^{[1
]}

Dong, Lingfang ^{[1
]}

Zhu, Yingli ^{[1
]}

Zhao, Ningmin ^{[1
]}

Qin, Yuhua ^{[1
]}

机构：

[1] Zhengzhou Univ, Peoples Hosp, Dept Pharm, 7 Weiwu Rd, Zhengzhou 450003, Henan, Peoples R China

[2] Zhengzhou Univ, Peoples Hosp, Dept Haematol, Zhengzhou, Henan, Peoples R China

来源：

XENOBIOTICA | 2017年 / 47卷 / 12期

关键词：

CYP2C19; CYP3A4; genetic polymorphisms; individualized medication; voriconazole; INVASIVE FUNGAL-INFECTIONS; ESCMID-ASTERISK GUIDELINE; CARE-UNIT PATIENTS; GENETIC POLYMORPHISMS; PLASMA-CONCENTRATIONS; ADULT PATIENTS; CYP2C19; PHARMACOKINETICS; CANDIDA; MANAGEMENT;

D O I：

10.1080/00498254.2016.1271960

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. Polymorphisms of cytochrome P450 2C19 (CYP2C19) is an important factor contributing to variability of voriconazole pharmacokinetics. Polymorphisms of CYP3A4, CYP3A5, CYP2C9 and non-genetic factors such as age, gender, body mass index (BMI), transaminase levels, concomitant medications might also affect voriconazole initial steady serum trough concentration (VICmin) in haematological patients, but the effects were not clear. 2. Eighteen single-nucleotide polymorphisms in CYP2C19, CYP3A4, CYP3A5, CYP2C9 were genotyped. Patients were stratified into two groups according to CYP2C19 genotype. Group 1 were patients with CYP2C19*2 or CYP2C19*3, and Group 2 were homozygous extensive metabolizers. The effects were studied in different groups. VICmin was adjusted on daily dose (VICmin/D) for overcoming effect of dose. 3. A total of 106 blood samples from 86 patients were included. In final optimal scaling regression models, polymorphisms of rs4646437 (CYP3A4), age, BMI was identified to be factors of VICmin/D in Group 1 (R-2=.255, p<.001). Only age was confirmed as a factor of VICmin/D in Group 2 (R-2 = 0.144, p = .021). 4. Besides polymorphisms of CYP2C19, in individualized medication of voriconazole in haematological patients, polymorphisms of CYP3A4, and non-genetic factors as BMI, age should also be taken into account, especially for individuals with CYP2C19*2 or CYP2C19*3.

引用

页码：1121 / 1129

页数：9

共 42 条

[1] High-throughput multiplex SNP genotyping with MALDI-TOF mass spectrometry: Practice, problems and promise [J].

Bray, MS ;

Boerwinkle, E ;

Doris, PA .

HUMAN MUTATION, 2001, 17 (04) :296-304

[2] Genetic polymorphism analysis of CYP2C19 in Chinese Han populations from different geographic areas of mainland China [J].

Chen, Lingling ;

Qin, Shengying ;

Xie, Jing ;

Tang, Jimin ;

Yang, Lun ;

Shen, Wen ;

Zhao, Xinzhi ;

Du, Jing ;

He, Guang ;

Feng, Guoyin ;

He, Lin ;

Xing, Qinghe .

PHARMACOGENOMICS, 2008, 9 (06) :691-702

[3] Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology [J].

Clendenen, Tess V. ;

Rendleman, Justin ;

Ge, Wenzhen ;

Koenig, Karen L. ;

Wirgin, Isaac ;

Currie, Diane ;

Shore, Roy E. ;

Kirchhoff, Tomas ;

Zeleniuch-Jacquotte, Anne .

PLOS ONE, 2015, 10 (08)

[4] CYP3A7, CYP3A5, CYP3A4, and ABCB1 Genetic Polymorphisms, Cyclosporine Concentration, and Dose Requirement in Transplant Recipients [J].

Crettol, Severine ;

Venetz, Jean-Pierre ;

Fontana, Massimiliano ;

Aubert, John-David ;

Pascual, Manuel ;

Eap, Chin B. .

THERAPEUTIC DRUG MONITORING, 2008, 30 (06) :689-699

[5] Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group [J].

De Pauw, Ben ;

Walsh, Thomas J. ;

Donnelly, J. Peter ;

Stevens, David A. ;

Edwards, John E. ;

Calandra, Thierry ;

Pappas, Peter G. ;

Maertens, Johan ;

Lortholary, Olivier ;

Kauffman, Carol A. ;

Denning, David W. ;

Patterson, Thomas F. ;

Maschmeyer, Georg ;

Bille, Jacques ;

Dismukes, William E. ;

Herbrecht, Raoul ;

Hope, William W. ;

Kibbler, Christopher C. ;

Kullberg, Bart Jan ;

Marr, Kieren A. ;

Munoz, Patricia ;

Odds, Frank C. ;

Perfect, John R. ;

Restrepo, Angela ;

Ruhnke, Markus ;

Segal, Brahm H. ;

Sobel, Jack D. ;

Sorrell, Tania C. ;

Viscoli, Claudio ;

Wingard, John R. ;

Zaoutis, Theoklis ;

Bennett, John E. .

CLINICAL INFECTIOUS DISEASES, 2008, 46 (12) :1813-1821

[6] Clinical significance of the cytochrome P4502C19 genetic polymorphism [J].

Desta, Z ;

Zhao, XJ ;

Shin, JG ;

Flockhart, DA .

CLINICAL PHARMACOKINETICS, 2002, 41 (12) :913-958

[7] Multicenter Study of Voriconazole Pharmacokinetics and Therapeutic Drug Monitoring [J].

Dolton, Michael J. ;

Ray, John E. ;

Chen, Sharon C. -A. ;

Ng, Kingsley ;

Pont, Lisa G. ;

McLachlan, Andrew J. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (09) :4793-4799

[8]

Dote S, 2016, J PHARM HEALTH CARE, V2, DOI 10.1186/s40780-016-0044-9

[9] Variability of Voriconazole Plasma Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Cytochrome P450 Polymorphisms and Comedications on Initial and Subsequent Trough Levels [J].

Gautier-Veyret, Elodie ;

Fonrose, Xavier ;

Tonini, Julia ;

Thiebaut-Bertrand, Anne ;

Bartoli, Mireille ;

Quesada, Jean-Louis ;

Bulabois, Claude-Eric ;

Cahn, Jean-Yves ;

Stanke-Labesque, Francoise .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (04) :2305-2314

[10] Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis [J].

Guery, Benoit P. ;

Arendrup, Maiken C. ;

Auzinger, Georg ;

Azoulay, Elie ;

Borges Sa, Marcio ;

Johnson, Elizabeth M. ;

Mueller, Eckhard ;

Putensen, Christian ;

Rotstein, Coleman ;

Sganga, Gabriele ;

Venditti, Mario ;

Zaragoza Crespo, Rafael ;

Kullberg, Bart Jan .

INTENSIVE CARE MEDICINE, 2009, 35 (01) :55-62

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