caa a22 4500 606157107 CHVBK 20210128100612.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10096-014-2294-5 doi (NATIONALLICENCE)springer-10.1007/s10096-014-2294-5 Effects of CYP3A4 polymorphisms on the plasma concentration of voriconazole [Elektronische Daten] [H.-R. He, J.-Y. Sun, X.-D. Ren, T.-T. Wang, Y.-J. Zhai, S.-Y. Chen, Y.-L. Dong, J. Lu] Voriconazole is frequently utilized for the prevention and treatment of invasive fungal infections (IFIs), and is extensively metabolized by the cytochrome P450 (CYP) system. The impact of activity of the genes encoding CYP3A4, CYP3A5, and CYP2C9 on the pharmacokinetics of voriconazole cannot be ignored because, second to CYP2C19, they are the most important enzymes involved in voriconazole metabolism. The influence of genetic polymorphisms in CYP3A4, CYP3A5, and CYP2C9 on the plasma concentrations of voriconazole was evaluated in the present study. The study cohort comprised 158 patients with IFIs in whom 22 single-nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, and CYP2C9 were genotyped using the Sequenom MassARRAY RS1000 system, and voriconazole plasma concentrations were measured by high-performance liquid chromatography (HPLC). 40, 91, and 27 patients presented with low (<1mg/L), normal (1-4mg/L), and high (>4mg/L) plasma voriconazole concentrations, respectively. Correlation analysis between polymorphisms and the plasma voriconazole concentration revealed an association between the presence of the rs4646437 T allele and a higher plasma voriconazole concentration [p = 0.033, odds ratio (OR) = 2.832, 95% confidence interval (CI) = 1.086-7.384]. This study has identified a new SNP related to the metabolism of voriconazole, potentially providing novel insight into the influence of CYP3A4 on the pharmacokinetics of this antifungal agent. Springer-Verlag Berlin Heidelberg, 2014 He H.-R Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut Sun J.-Y Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut Ren X.-D Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut Wang T.-T Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut Zhai Y.-J Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut Chen S.-Y Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut Dong Y.-L Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut Lu J. Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/4(2015-04-01), 811-819 0934-9723 34:4<811 2015 34 10096 https://doi.org/10.1007/s10096-014-2294-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10096-014-2294-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- He H.-R Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 700 1- Sun J.-Y Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 700 1- Ren X.-D Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 700 1- Wang T.-T Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 700 1- Zhai Y.-J Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 700 1- Chen S.-Y Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 700 1- Dong Y.-L Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 700 1- Lu J. Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061, Xi'an, People's Republic of China aut NATIONALLICENCE 773 0- European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/4(2015-04-01), 811-819 0934-9723 34:4<811 2015 34 10096