A Perspective Study on Therapeutic Drug Monitoring of Voriconazole in Pediatric Patients with Hematologic Disorders

Pub Date : 2024-07-17 DOI:10.5812/jjm-146488
Sedigheh Barzegar, Ali Amanati, Fatemeh Ghasemi, H. Jafarian, P. Badiee
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Abstract

Background: The incidence of invasive aspergillosis and the administration of voriconazole have risen among immunocompromised patients. Objectives: This study aimed to evaluate serum voriconazole concentration and its corresponding influential factors in pediatric patients with hematologic disorders. Methods: A total of 132 blood samples were collected from 44 pediatric patients with hematologic disorders infected with invasive aspergillosis and treated with voriconazole. Among these patients, 20.5% were classified as having proven invasive aspergillosis, 77.2% as probable, and 2.3% as possible. Voriconazole serum levels were evaluated using HPLC on the 3rd, 5th, and 7th days of treatment. Genotyping of the CYP2C19 alleles (*2, *3, and *17) was performed, and demographic and clinical data were gathered from records between 2018 to 2020. Results: The voriconazole concentration in 70.5% of patients and 77.3% of treatment cases (complete or partial) ranged from 1 to 5.5 µg/mL. Adverse events were observed in 4.5% of the patients. Genotyping of CYP2C19 genes revealed CYP2C1911 (5.4%), CYP2C19117 (16.2%), CYP2C1912 (51.4%), and CYP2C19217 (27%). Multivariate analysis using linear regression demonstrated that serum voriconazole concentration increased by 0.037 µg/mL per year of age and by 0.06 µg/mL for each unit increase in C-reactive protein (on the 3rd day of voriconazole therapy). Additionally, an increase in alanine aminotransferase level by 1 unit decreased the mean voriconazole concentration by 0.03 µg/mL. Of these patients, 65.9% were completely treated, 11.4% were partially treated, and 22.7% died. Conclusions: Serum voriconazole concentrations varied among pediatric hematologic patients receiving standard doses, with age, C-reactive protein, and alanine aminotransferase levels affecting the concentration of voriconazole in the sera of pediatric patients.
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关于血液病儿科患者中伏立康唑治疗药物监测的透视研究
背景:在免疫力低下的患者中,侵袭性曲霉菌病的发病率和伏立康唑的使用率都有所上升。研究目的本研究旨在评估血液病儿科患者的血清伏立康唑浓度及其相应的影响因素。研究方法共收集了 44 名感染侵袭性曲霉菌病并接受伏立康唑治疗的血液病儿科患者的 132 份血样。在这些患者中,20.5%被归类为已证实患有侵袭性曲霉菌病,77.2%为可能,2.3%为可能。在治疗的第 3 天、第 5 天和第 7 天,使用高效液相色谱法评估伏立康唑的血清水平。对CYP2C19等位基因(*2、*3和*17)进行了基因分型,并从2018年至2020年的记录中收集了人口统计学和临床数据。结果:70.5%的患者和77.3%的治疗病例(完全或部分)的伏立康唑浓度在1至5.5微克/毫升之间。4.5%的患者出现了不良反应。CYP2C19 基因的基因分型显示有 CYP2C1911(5.4%)、CYP2C19117(16.2%)、CYP2C1912(51.4%)和 CYP2C19217(27%)。使用线性回归进行的多变量分析表明,年龄每增加一岁,血清伏立康唑浓度增加 0.037 微克/毫升;C 反应蛋白每增加一个单位,血清伏立康唑浓度增加 0.06 微克/毫升(伏立康唑治疗的第 3 天)。此外,丙氨酸氨基转移酶水平每增加 1 个单位,伏立康唑的平均浓度就会降低 0.03 µg/mL。在这些患者中,65.9%完全治愈,11.4%部分治愈,22.7%死亡。结论接受标准剂量治疗的儿科血液病患者血清中伏立康唑的浓度各不相同,年龄、C反应蛋白和丙氨酸氨基转移酶水平会影响儿科患者血清中伏立康唑的浓度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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