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印度南部人群细胞色素 P450 3A5(CYP3A5)遗传多态性对卡马西平剂量调整后血浆水平的影响。

Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on dose-adjusted plasma levels of carbamazepine in epileptic patients in South Indian population.

机构信息

Department of Pharmacology, JIPMER, Puducherry, India.

Department of Neurology, JIPMER, Puducherry, India.

出版信息

Indian J Pharmacol. 2019 Nov-Dec;51(6):384-388. doi: 10.4103/ijp.IJP_122_19. Epub 2020 Jan 16.

Abstract

AIM

The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 genotypes.

SUBJECTS AND METHODS

The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of was done using real-time polymerase chain reaction method.

RESULTS

Patients inheriting variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either or (expressers) (4.3 μg/ml, = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers ( < 0.002 and < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively.

CONCLUSION

There is a significant influence of genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population.

摘要

目的

本研究旨在比较 CYP3A5 基因型表达者和非表达者的卡马西平(CBZ)剂量调整血浆水平。

受试者和方法

该研究在 100 名接受 CBZ 单药治疗的癫痫患者中进行。使用反相高效液相色谱法测定稳态血浆 CBZ 水平,并使用实时聚合酶链反应法进行 基因分型。

结果

与遗传 或 (表达者)的患者(4.3μg/ml,=0.004)相比,遗传 变异型(非表达者)的患者 CBZ 血浆浓度升高(4.86μg/ml)。与表达者相比,非表达者在调整剂量和体重后,CBZ 的血浆浓度显著升高(分别为 <0.002 和 <0.001)。表达者和非表达者的不良反应发生率分别为 12%和 9%。

结论

在印度南部人群中,CYP3A5 基因多态性(6986A>G)对癫痫患者 CBZ 的剂量调整血浆水平有显著影响。

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