| Title | Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections |
| Authors | Wang, Taotao Zhu, Huifang Sun, Jinyao Cheng, Xiaoliang Xie, Jiao Dong, Haiyan Chen, Limei Wang, Xue Xing, Jianfeng Dong, Yalin |
| Affiliation | Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Dept Pharm, Xian 710061, Peoples R China. Tengzhou Cent Peoples Hosp, Dept Pharm, Tengzhou 277500, Peoples R China. Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100871, Peoples R China. Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Dept Hematol, Xian 710061, Peoples R China. Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Cent Intens Care Unit, Xian 710061, Peoples R China. Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, Xian 710061, Peoples R China. |
| Keywords | Voriconazole Efficacy Safety Hepatotoxicity CYP2C19 Trough plasma concentrations INTRAVENOUS VORICONAZOLE ANTIFUNGAL AGENT PHARMACOKINETICS MULTICENTER IDENTIFICATION GENOTYPE TRIAZOLE |
| Issue Date | 2014 |
| Publisher | international journal of antimicrobial agents |
| Citation | INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS.2014,44,(5),436-442. |
| Abstract | The aim of this study was to determine an optimum voriconazole target concentration, to study the influence of CYP2C19 gene status on metabolism of voriconazole and to identify a dose-adjustment strategy for voriconazole according to CYP2C19 polymorphism in patients with invasive fungal infections. A total of 328 voriconazole trough plasma concentrations (C-min) were collected and monitored from 144 patients. Information on efficacy and safety was obtained. Voriconazole therapy was effective in 81.9% of patients (118/144), and 12.5% (18/144) exhibited signs of hepatotoxicity. The relationships between voriconazole C-min and clinical response and hepatotoxicity were explored using logistic regression, and a target clinical C-min range of 1.5-4 mg/L was identified. Values of voriconazole C-min and the ratio of C-min to concentration of voriconazole-N-oxide ( Cmin/CN) of poor metabolisers (PMs) were significantly higher than extensive metabolisers and intermediate metabolisers. Model-based simulations showed that PM patients could be safely and effectively treated with 200 mg twice daily orally or intravenously, and non-PM patients with 300 mg twice daily orally or 200 mg twice daily intravenously. This study highlighted that voriconazole C-min and C-min/C-N are strongly influenced by CYP2C19 polymorphism, and gene-adjusted dosing is important to achieve therapeutic levels that maximise therapeutic response and minimise hepatotoxicity. (C) 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/189115 |
| ISSN | 0924-8579 |
| DOI | 10.1016/j.ijantimicag.2014.07.013 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
