伏立康唑基因多态性与血药浓度的研究进展

Research Progress on the Relationship between Voriconazole Genetic Polymorphisms and Blood Drug Concentrations

伏立康唑(Voriconazole,VRZ)是一种广谱抗真菌药物,广泛用于治疗侵袭性真菌感染。然而,VRZ的药代动力学特性存在显著个体差异,包括非线性药代动力学和不良反应。基因多态性,特别是与CYP酶相关的基因多态性,对VRZ的代谢速率和血药浓度有显著影响。在VRZ治疗过程中,根据个体基因型和血药浓度调整药物剂量至关重要。本研究综述了VRZ治疗窗和不良反应等问题,强调基因多态性在VRZ药代动力学和药效学中的关键作用。特别分析了CYP家族基因(如CYP2C19、CYP2C9、CYP3A)、POR基因、FMO3基因以及转运蛋白基因(如SLCO2B1、ABCB1)多态性对VRZ血药浓度及个体化治疗策略的影响,为VRZ的个体化治疗提供科学依据,减少不良反应,提升治疗效果,并为未来研究指明方向。

Voriconazole(VRZ)is a broad-spectrum antifungal drug widely used to treat aggressive fungal infections.However,there are significant individual differences in the pharmacokinetic characteristics of VRZ,including nonlinear pharmacokinetics and high adverse reaction rates.Gene polymorphisms,especially those related to CYP enzyme,have significant effects on the metabolic rate and blood concentration of VRZ.During VRZ treatment,it is important to adjust the drug dose according to the individual genotype and blood concentration.In this study,the narrow therapeutic window and high incidence of adverse reactions of VRZ were discussed,emphasizing the key role of gene polymorphism in the pharmacokinetics and pharmacodynamics of VRZ.In particular,the effects of polymorphisms of CYP family genes(such as CYP2C19,CYP2C9,CYP3A),POR genes,FMO3 genes,and transporter genes(such as SLCO2B1,ABCB1)on VRZ blood concentration and individual therapy strategies were analyzed.The aim is to provide scientific basis for the individualized treatment of VRZ by summarizing the current research results,reduce the adverse reactions,improve the therapeutic effect,and point out the direction for future research.