Factors Influencing Blood Concentration of Voriconazole and Therapeutic Drug Monitoring in Patients with Child–Pugh Class C Cirrhosis

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Ying Zhang, Rongrong Wu, Fangfang Liu, Yonggang Wang, Junchang Zhang, Chengcheng Ji, Xianghong Lu, D. Chang, J. Mu
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Abstract

What Is Known and Objective. CYP2C19 is an important influencing factor for voriconazole trough plasma concentration (Cmin); however, it is not verified in Child–Pugh C (CP-C) cirrhosis patients, and no voriconazole dosage regimen is recommended for these patients in the package insert. This retrospective study identified CYP2C19 and other factors influencing voriconazole Cmin for CP-C cirrhosis, and obtained an appropriate method of application of voriconazole for them. Methods. A total of 66 patients with CP-C cirrhosis who accepted voriconazole therapy were involved. The voriconazole Cmin, clinical characteristics, CYP2C19 genotype, and adverse effects (AEs) were recorded and analyzed. Results. Unlike other research studies, voriconazole Cmin was not different among normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs) of the CYP2C19 enzyme in CP-C cirrhosis ( P  > 0.05). The maintenance dose regimen for voriconazole was the only independent influencing factor for Cmin ( P  = 0.045; OR = 3.753; 95% CI, 1.029–13.694). At about 1/3 of the recommended maintenance dose, only 16.7% (8/48) had Cmin >5.5 μg/mL, 4.5% (3/48) had Cmin <1 μg/mL, and only one AE happened. There were four voriconazole-related AEs that happened in this study, and three AEs occurred (3/4, 75%) when the maintenance dose was not adjusted with therapeutic drug monitoring (TDM). What Is New and Conclusion. Voriconazole Cmin did not significantly vary according to CYP2C19 enzyme metabolization status (being an NM, IM, or PM) in CP-C cirrhosis. Reducing the maintenance dose of voriconazole to approximately 1/3 the standard maintenance dose and administering in combination with TDM in patients with CP-C cirrhosis are recommended.
Child-Pugh C级肝硬化患者伏立康唑血药浓度的影响因素及治疗药物监测
什么是已知的和客观的。CYP2C19是伏立康唑谷血浆浓度(Cmin)的重要影响因素;然而,它没有在Child-Pugh C(CP-C)肝硬化患者中得到验证,包装说明书中不建议这些患者使用伏立康唑给药方案。本回顾性研究确定了CYP2C19和其他影响伏立康唑Cmin治疗CP-C肝硬化的因素,并获得了一种合适的伏立康唑应用方法。方法。共有66例CP-C肝硬化患者接受伏立康唑治疗。记录并分析伏立康唑Cmin、临床特征、CYP2C19基因型和不良反应。后果与其他研究不同,伏立康唑Cmin在CP-C肝硬化CYP2C19酶的正常代谢者(NMs)、中间代谢者(IM)和不良代谢者(PM)之间没有差异(P > 伏立康唑维持剂量方案是Cmin的唯一独立影响因素(P = 0.045;或 = 3.753;95%可信区间,1.029–13.694)。在约推荐维持剂量的1/3时,只有16.7%(8/48)的Cmin>5.5 μg/mL,4.5%(3/48)的Cmin<1 μg/mL,仅发生1例AE。本研究共发生4例伏立康唑相关AE,其中3例(3/4,75%)在维持剂量未经治疗药物监测(TDM)调整时发生。新内容和结论。在CP-C肝硬化中,伏立康唑Cmin根据CYP2C19酶代谢状态(NM、IM或PM)没有显著变化。建议CP-C肝硬化患者将伏立康唑的维持剂量降至标准维持剂量的约1/3,并与TDM联合用药。
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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