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血药浓度监测联合CYP2C19 基因多态性检测对伏立康唑治疗婴幼儿侵袭性真菌感染个体化给药的临床价值
韩雪,董静,潘梦瑾,高晓静,崔建坡
0
(河南省开封市儿童医院,河南开封 475000)
摘要:
目的:评估血药浓度监测联合CYP2C19 基因多态性检测在伏立康唑治疗2 岁以下婴幼儿侵袭性真菌感染个体化给药治 疗中的应用价值。方法:选取2022 年8 月-2024 年1 月河南省开封市儿童医院收治的侵袭性真菌感染患儿30 例,根据伏立康 唑血药浓度与CYP2C19 基因多态性结果进行分析。根据基因检测代谢类型分为快代谢型、中代谢型与慢代谢型,并评估 CYP2C19 基因多态性与伏立康唑血药谷浓度安全性及有效性的关系。结果:共纳入侵袭性真菌感染患儿30 例,男女比例 1 ∶ 1,患儿年龄均<2 岁,体质量(9. 01±6. 22) kg,公斤体质量日剂量(8. 25±0. 71) mg/ kg,稳态血药谷浓度(2. 65±0. 43) mg/ L。 快代谢组、中代谢组与慢代谢组患儿任意两组公斤体质量日剂量比较差异无统计学意义(P>0. 05)。快代谢组、中代谢组与慢 代谢组患儿稳态血药谷浓度、谷浓度达标率比较差异有统计学意义(P<0. 05)。中代谢组与慢代谢组患儿稳态血药谷浓度均明 显高于快代谢组,中代谢组与慢代谢组患儿谷浓度达标率均明显高于快代谢组,慢代谢组患儿稳态血药谷浓度明显高于中代谢 组,差异均有统计学意义(P<0. 05)。慢代谢组患儿不良反应总发生率高于快代谢组、中代谢组(P<0. 05)。结论:伏立康唑治 疗2 岁以下婴幼儿侵袭性真菌感染的疗效与CYP2C19 基因多态性有关,结合血药浓度监测有助于指导个体化给药及提高用药 安全性。
关键词:  侵袭性真菌感染  伏立康唑  血药浓度  CYP2C19  基因多态性
DOI:10.13407/j.cnki.jpp.1672-108X.2024.12.003
基金项目:2022 年度开封市科技发展计划项目,编号2203106。
Henan Kaifeng Children’ s Hospital, Henan Kaifeng  475000, China
Han Xue, Dong Jing, Pan Mengjin, Gao Xiaojing, Cui Jianpo
(Henan Kaifeng Children’ s Hospital, Henan Kaifeng   475000, China)
Abstract:
Objective: To evaluate the application value of blood concentration monitoring combined with CYP2C19 gene polymorphism detection in individualized treatment of invasive fungal infection in infants under 2 years with voriconazole. Methods: Totally 30 children with invasive fungal infection admitted into Henan Kaifeng Children’s Hospital from Aug. 2022 to Jan. 2024 were extracted. Results of voriconazole blood concentration and CYP2C19 gene polymorphism were analyzed. The metabolic types were divided into the fast metabolism type, medium metabolism type and slow metabolism type. The correlation between CYP2C19 gene polymorphism and safety and efficacy of voriconazole blood trough concentration was evaluated. Results: A total of 30 children with invasive fungal infection were enrolled, with a male to female ratio of 1 ∶ 1. The age of the child was <2 years, the body mass was (9. 01±6. 22) kg, the daily per kg dose was (8. 25±0. 71) mg/ kg, and the steady-state blood trough concentration was (2. 65±0. 43) mg/ L. The daily per kg dose among the fast metabolism group, medium metabolism group and slow metabolism group was not statistically significant (P>0. 05). The steadystate blood drug trough concentration and compliance rate of trough concentration among the fast metabolism group, medium metabolism group and slow metabolism group were statistically significant (P<0. 05). The steady-state blood drug trough concentration of children in the medium metabolism group and slow metabolism group was significantly higher than that in the fast metabolism group, the compliance rate of trough concentration in the medium metabolism group and slow metabolism group was significantly higher than that in the fast metabolism group, the steady-state blood drug trough concentration in the slow metabolism group was significantly higher than that in the medium metabolism group, with statistically significant differences (P<0. 05). The total incidence of adverse drug reactions in the slow metabolism group was higher than that in the fast metabolism group and medium metabolism group (P<0. 05). Conclusion: The efficacy of voriconazole in the treatment of invasive fungal infection in infants under 2 years is related to CYP2C19 gene polymorphism, and the combination with blood concentration monitoring is helpful to guide individualized drug administration and improve drug safety.
Key words:  Henan Kaifeng Children’ s Hospital, Henan Kaifeng  475000, China

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