Prospective Analysis of Factors Influencing Inter-Individual Variation in Trough Plasma Voriconazole Concentrations in Older Patients-Impact of High α1-Acid Glycoprotein Levels.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yukako Yasui, Hiroyuki Yasui, Yoshiki Yamamoto, Toshihiko Ishizaka, Kazuo Hatanaka, Waki Imoto, Wataru Shibata, Koichi Yamada, Hiroshi Kakeya
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引用次数: 0

Abstract

Voriconazole (VRCZ), an azole-based, deep-seated antifungal agent, is used as a 1st-line treatment for aspergillosis in Japan. VRCZ exhibits nonlinear pharmacokinetic (PK) behavior with relatively large inter-individual variability in plasma concentration. Additionally, genetic polymorphisms of CYP2C19 have been reported to influence the metabolic variability of VRCZ. The purpose of this study was to search for and identify clinically relevant potential factors influencing the PK and plasma concentration of VRCZ to better inform VRCZ dosing regimens. Thirty patients receiving VRCZ were enrolled. Total (Ct) and unbound (Cu) trough plasma concentrations of VRCZ were determined by the HPLC-UV method. Univariate and multivariate correlation analyses were used to evaluate the relationships between Ct or Ct/dose per body weight (Ct/D) and individual demographic and laboratory characteristics. Since the increasing trend of C-reactive protein (CRP) inversely correlated with the classification of CYP2C19 gene polymorphisms, it was suggested that the inflammation counteracted the trend of Ct according to CYP2C19 gene polymorphisms. Spearman's rank-order correlation analysis showed significant correlations between Ct and dose per body weight, CRP, and α1-acid glycoprotein (α1-AGP). Multivariate linear regression analysis showed that age, dose per body weight, CRP, and α1-AGP were significant explanatory factors for Ct. In particular, elevated α1-AGP levels were found to have significant explanatory value for decreased Ct. Although the present study has critical limitations, such as the patient sample was small in size and being limited to a single medical institution, this finding may explain some of the inter-individual variability in plasma VRCZ concentration.

老年患者伏立康唑谷血药浓度个体差异影响因素的前瞻性分析——高α1-酸性糖蛋白水平的影响
伏立康唑(Voriconazole, VRCZ)是一种以唑为基础的深层抗真菌药物,在日本被用作治疗曲霉病的一线药物。VRCZ表现出非线性药代动力学(PK)行为,血浆浓度具有较大的个体间差异。此外,CYP2C19的遗传多态性已被报道影响VRCZ的代谢变异性。本研究的目的是寻找并识别影响VRCZ药代动力学和血药浓度的临床相关潜在因素,以便更好地为VRCZ给药方案提供依据。30例接受VRCZ治疗的患者入组。采用HPLC-UV法测定VRCZ的总(Ct)和未结合(Cu)槽血药浓度。采用单因素和多因素相关分析评估Ct或Ct/剂量/体重(Ct/D)与个体人口学和实验室特征之间的关系。由于c反应蛋白(CRP)的升高趋势与CYP2C19基因多态性的分类呈负相关,提示炎症根据CYP2C19基因多态性抵消了Ct的升高趋势。Spearman秩序相关分析显示Ct与单位体重剂量、CRP、α1-酸性糖蛋白(α1-AGP)有显著相关性。多因素线性回归分析显示,年龄、单位体重剂量、CRP、α1-AGP是Ct的显著解释因素。特别是α - 1- agp水平升高对Ct降低具有显著的解释价值。尽管目前的研究存在严重的局限性,例如患者样本规模小且仅限于单一医疗机构,但这一发现可能解释了血浆VRCZ浓度的一些个体间差异。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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