The Impact of Plasma Protein Binding Characteristics and Unbound Concentration of Voriconazole on Its Adverse Drug Reactions
The Impact of Plasma Protein Binding Characteristics and Unbound Concentration of Voriconazole on Its Adverse Drug Reactions
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伏立康唑血浆蛋白结合特性及游离浓度对其不良反应的影响
DOI：
10.3389/fphar.2020.00505
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发表时间：
2020-04-24
影响因子：
5.6
通讯作者：
Wang, Yong-Qing
中科院分区：
文献类型：
--
作者：
Yuan, Zi-Qing-Yun;Qiao, Chun;Wang, Yong-Qing
研究恶性血液病患者伏立康唑(VRC)游离血药浓度及其与药物不良反应(ADRs)的关系。血浆样本从患者身上采集或在体外添加。采用高效液相色谱-串联质谱仪(LC-MS/MS)分析药物浓度，采用快速平衡透析法分离游离VRC和结合VRC。肝功能和治疗细节从患者的电子病历中收集。蛋白质浓度按说明书进行测定。患者的VRC血浆蛋白结合率(PPB)[69.5±6.2%]明显高于体外标本，受药物总浓度(Ct)、血浆蛋白浓度和蛋白类型的影响。α1-酸性糖原与VRc的亲和力最强。VRC的总PPB与单个蛋白质的PPB之间不是简单的相加关系，而是一个压缩组合。VRC的游离药物浓度(Cu)与Ct、蛋白质浓度、AST水平、CYP2C19代谢类型及合用高PPB药物有显著相关性。VRC游离血药浓度与ADRs的关系比Ct更敏感。
This study investigated voriconazole (VRC) unbound plasma concentration and its relationship with adverse drug reactions (ADRs) in patients with malignant hematologic disease. Plasma samples were collected from patients or spiked in vitro. A time-saving rapid equilibrium dialysis assay was used for the separation of unbound and bound VRC, following a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis method for drug concentration detection. Liver function and treatment details were collected from the electronic medical records of patients. Protein concentration was determined according to instructions. VRC plasma protein binding rate (PPB) in patient is significantly higher [69.5 ± 6.2%] than that in in-vitro samples, influenced by total drug concentration (Ct), plasma protein concentration, and protein type. The α1-acid glycogen (AAG) has the highest affinity with VRC. Relationship between total PPB of VRC with PPB of individual protein is not a simple addition, but a compressive combination. Unbound drug concentration (Cu) of VRC shows significant relationships with Ct, protein concentration, AST level, metabolism type of CYP2C19 and co-administration of high PPB medicines. Unbound plasma concentration of VRC shows a more sensitive relationship with ADRs than Ct.