Impact of CYP2C19, CYP2C9, CYP3A4, and FMO3 Genetic Polymorphisms and Sex on the Pharmacokinetics of Voriconazole after Single and Multiple Doses in Healthy Chinese Subjects.
Voriconazole is the first‐line treatment for invasive aspergillosis. Its pharmacokinetics exhibit considerable inter‐ and intra‐individual variability. The purpose of this study was to investigate the effects of CYP2C19, CYP2C9, CYP3A4, and FMO3 genetic polymorphisms and sex on the pharmacokinetics...
| Publicado en: | Journal of Clinical Pharmacology Vol. 64; no. 8; pp. 1030 - 1044 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Aug2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=178683604&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 178683604 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Aug2024 vid: 64 iid: 8 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 178683604 176779909 178683604 178683604 10.1002/jcph.2440 178683604 ppf: 1030 ppct: 14 formats: tig: atl: Impact of CYP2C19, CYP2C9, CYP3A4, and FMO3 Genetic Polymorphisms and Sex on the Pharmacokinetics of Voriconazole after Single and Multiple Doses in Healthy Chinese Subjects. aug: au: Liu, Shuaibing Yao, Xia Tao, Jun Zhao, Shiyu Sun, Suke Wang, Suyun Tian, Xin affil: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou Henan Province,, China sug: subj: Voriconazole Pharmacokinetics Voriconazole Administration and Dosage Aspergillosis Drug Therapy Polymorphism, Genetic Chinese Persons In Adulthood Oxidoreductases Drug Efficacy Individualized Medicine Genotype Sex Factors Human Male Female Adolescence Adult Middle Age China Descriptive Statistics Hereditary Diseases Funding Source Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Voriconazole is the first‐line treatment for invasive aspergillosis. Its pharmacokinetics exhibit considerable inter‐ and intra‐individual variability. The purpose of this study was to investigate the effects of CYP2C19, CYP2C9, CYP3A4, and FMO3 genetic polymorphisms and sex on the pharmacokinetics of voriconazole in healthy Chinese adults receiving single‐dose and multiple‐dose voriconazole, to provide a reference for its clinical individualized treatment. A total of 123 healthy adults were enrolled in the study, with 108 individuals and 15 individuals in the single‐dose and multiple‐dose doses, respectively. Plasma voriconazole concentrations were measured using a validated LC‐MS/MS method, and pharmacokinetics parameters were calculated using the non‐compartmental method with WinNonlin 8.2. CYP2C19, CYP2C9, CYP3A4, and FMO3 single‐nucleotide polymorphisms were sequenced using the Illumina Hiseq X‐Ten platform. The results suggested that CYP2C19 genetic polymorphisms significantly affected the pharmacokinetics of voriconazole at single doses of 4, 6, and 8 mg/kg and multiple doses of voriconazole. CYP3A4 rs2242480 had a significant effect on AUC0‐∞ (area under the plasma concentration‐time curve from time 0 to infinity) and MRT (mean residence time) of voriconazole at a single dose of 4 mg/kg in CYP2C19 extensive metabolizer. Regardless of the CYP2C19 genotype, CYP2C9 rs1057910 and FMO3 rs2266780 were not associated with the pharmacokinetics of voriconazole at three single‐dose levels or multiple doses. No significant differences in most voriconazole pharmacokinetics parameters were noted between male and female participants after single and multiple dosing. For patients receiving voriconazole treatment, CYP2C19 genetic polymorphisms should be genotyped for its precision administration. In contrast, based on our study of healthy Chinese adults, it seems unnecessary to consider the effects of CYP2C9, CYP3A4, and FMO3 genetic polymorphisms on voriconazole pharmacokinetics. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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