Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients.
Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients.
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DOI：
10.3389/fphar.2022.833303
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发表时间：
2022
影响因子：
5.6
通讯作者：
Zhang, Xiaojian
中科院分区：
文献类型：
--
作者：
Jia, Mengmeng;Zhang, Qiwen;Qin, Zifei;Wang, Dao;Liu, Peng;Yang, Jing;Zhang, Xiaojian
关键词：
泊沙康唑(PCZ)在儿科患者中的临床应用经验有限，也没有具体的剂量推荐。本研究旨在探讨一种合适的给药方案，并评估儿童中PCZ的暴露-反应关系。我们回顾了接受PCZ浓度监测的18岁住院患者的医疗记录。收集临床资料、PCZ剂量和监测数据。总共包括来自105名儿科患者的375个PCZ谷浓度(C Min)。在接受预防的儿童中，6岁、6-12岁和12岁的儿童达到治疗范围所需的中位剂量分别为14.80、14.52和12.90 mg/kg/天(p=0.001)；接受治疗的儿童的中位剂量分别为23.50、20.96和15.38 mg/kg/天(p=0.001)。在接受PCZ预防的儿童中，12%的儿童出现了已证实或可能突破的IFI；PCZ浓度的中位数显著低于那些治疗有效的儿童(0.43vs.1.20g/mlμ−1；p<；0.001)。接受PCZ治疗的79.2%的患者临床反应为阳性，且PCZ的中位数浓度显著高于病情进展的儿童(1.06vs0.53g/mLPCZ/μ−1；p=0.024)。未观察到C_(Min)值与肝毒性之间的关系。年龄、C反应蛋白、丙氨酸氨基转移酶和联合应用质子泵抑制剂等因素对PCZ C min有显著影响。有必要根据PCZ-C-min调整给药方案，使抗真菌药物个体化，为儿童用药调整提供指导。
Experience in the clinical use of posaconazole (PCZ) in pediatric patients is limited, and no specific dose recommendations exist. This study aimed to investigate an appropriate dosing regimen, and assess the exposure-response relationships of PCZ in children. We reviewed the medical records of inpatients aged <18 years who subjected to PCZ concentrations monitoring. Clinical data, PCZ dosing and monitoring data were collected. A total of 375 PCZ trough concentrations (C min) from 105 pediatric patients were included. For children receiving PCZ for prophylaxis, the median doses required to achieve the therapeutic range at the ages of <6, 6–12 and >12 years were 14.80, 14.52 and 12.90 mg/kg/day, respectively (p = 0.001); and for those receiving PCZ for treatment, the median doses were 23.50, 20.96 and 15.38 mg/kg/day, respectively (p = 0.001). Among children taking PCZ for prophylaxis, 12% developed a proven or probable breakthrough IFIs; the median PCZ concentrations were significantly lower than those children with successful treatment response (0.43 versus 1.20 μg mL−1; p < 0.001). 79.2% patients taking PCZ for treatment had a positive clinical response, and the median PCZ concentrations were significantly higher than those children with disease progression (1.06 versus 0.53 μg mL−1; p = 0.024). No association between C min values and hepatotoxicity was observed. Factors such as age, CRP, ALT and co-administration with proton pump inhibitors exhibited significant effects on PCZ C min. It is necessary to adjust the dosing regimens based on PCZ C min to individualize antifungal therapy and provide guidelines for dose adjustment in children.
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影响因子：
2.1
作者：
Chau, M. M.;Kong, D. C. M.;Worth, L. J.
通讯作者：
Worth, L. J.
影响因子：
6.7
作者：
Jang, S. H.;Colangelo, P. M.;Gobburu, J. V. S.
通讯作者：
Gobburu, J. V. S.
影响因子：
5.2
作者：
Lai, Tony;Alffenaar, Jan-Willem;Roberts, Jason A.
通讯作者：
Roberts, Jason A.
影响因子：
5.7
作者：
Vicenzi, Edoardo Bruno;Cesaro, Simone
通讯作者：
Cesaro, Simone
影响因子：
4.5
作者：
Boonsathorn S;Cheng I;Kloprogge F;Alonso C;Lee C;Doncheva B;Booth J;Chiesa R;Irwin A;Standing JF
通讯作者：
Standing JF