Effects of cytochrome P450 3A4 and non-genetic factors on initial voriconazole serum trough concentrations in hematological patients with different cytochrome P450 2C19 genotypes. (2nd December 2017)

• Record Type: Journal Article
• Authors: Shao, Beibei; Ma, Yongcheng; Li, Qiaoyan; Wang, Yimeng; Zhu, Zunmin; Zhao, Hongwei; Sun, Jun; Dong, Lingfang; Zhu, Yingli; Zhao, Ningmin; Qin, Yuhua
• Is Part Of: Xenobiotica. Volume 47:Number 12(2017)
• Page Start: 1121
• Page End: 1129
• Publication Date: 2017-12-02
• Subjects: CYP2C19 -- CYP3A4 -- genetic polymorphisms -- individualized medication -- voriconazole; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2016.1271960
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 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.