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依法韦仑剂量减少:一项描述成本效益、药代动力学和药物遗传学的观察性研究。

Dose reduction of efavirenz: an observational study describing cost-effectiveness, pharmacokinetics and pharmacogenetics.

作者信息

Martín Almudena Sánchez, Gómez Alicia Iglesias, García-Berrocal Belén, Figueroa Salvador Cabrera, Sánchez Miguel Cordero, Calvo Hernández María Victoria, Gonzalez-Buitrago Jose Manuel, Valverde Merino María Paz, Tovar Carmen Bustos, Martín Aurelio Fuertes, Isidoro-García María

机构信息

Servicio de Farmacia, Hospital Univeristario de Salamanca, Spain.

出版信息

Pharmacogenomics. 2014 May;15(7):997-1006. doi: 10.2217/pgs.14.48.

Abstract

AIM

Antiretroviral treatment implies a high cost to the healthcare system. The aim of this study was to evaluate the clinical and economic impact of efavirenz (EFV) dose adjustment by monitoring plasma concentrations and pharmacogenetic analysis of the 516G>T CYP2B6 polymorphism.

MATERIALS & METHODS: One hundred and ninety HIV patients treated with EFV were studied. Plasma EFV concentrations were measured by HPLC with ultraviolet detection, and pharmacogenetic analysis was performed by Real Time (RT)-PCR.

RESULTS

One hundred and ninety patients initially treated with a standard dose of EFV (600 mg/day) were studied. In 31 (16.3%) patients, EFV dose was reduced. A total of 87.1% of patients were heterozygous/homozygous carriers (GT/TT). CD4(+) count increased while the minimum steady-state plasma concentration and adverse effects decreased significantly after dose adjustment. Considering only the dose reduction, the adjustments accounted for a saving of 43,539 €/year.

CONCLUSION

The individualization of EFV dosage guided by genotyping 516G>T CYP2B6 and therapeutic drug monitoring could increase the efficiency of EFV use in antiretroviral treatment.

摘要

目的

抗逆转录病毒治疗给医疗系统带来高昂成本。本研究旨在通过监测血浆浓度以及对516G>T CYP2B6基因多态性进行药物遗传学分析,评估依非韦伦(EFV)剂量调整的临床和经济影响。

材料与方法

对190例接受EFV治疗的HIV患者进行研究。采用高效液相色谱法结合紫外检测测定血浆EFV浓度,并通过实时(RT)-PCR进行药物遗传学分析。

结果

对190例最初接受标准剂量EFV(600毫克/天)治疗的患者进行研究。31例(16.3%)患者的EFV剂量降低。共有87.1%的患者为杂合子/纯合子携带者(GT/TT)。剂量调整后,CD4(+)细胞计数增加,同时最低稳态血浆浓度和不良反应显著降低。仅考虑剂量降低,这些调整每年节省43,539欧元。

结论

通过对516G>T CYP2B6进行基因分型和治疗药物监测来实现EFV剂量个体化,可提高抗逆转录病毒治疗中EFV的使用效率。

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