[西泊尼莫德(BAF312):药物基因组剂量在治疗活动性继发性进行性多发性硬化症中的一般特征和临床意义]。

Susan Calfunao, Matías Carrasco, Carolina Gutierrez, Leslie Cerpa, Nelson Varela, Luis Quiñones
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引用次数: 0

摘要

西泊尼莫德是一种选择性免疫抑制剂,是第一种用于治疗活动性继发性进展型多发性硬化症的口服药物。这种药物通过调节磷酸鞘氨醇 1(S1P)受体,作为 S1P1 和 S1P5 的拮抗剂发挥作用,从而阻止淋巴细胞从淋巴结排出,防止中枢神经系统中引发脱髓鞘的炎症过程。有关患者用药的大量科学知识将取决于患者的药物遗传学特征。因此,美国食品和药物管理局强烈建议对代谢西泊莫德的酶 CYP2C9 进行基因分型研究,其基因变异 *2 和 *3 可将患者划分为代谢差、代谢广或代谢快的患者。CYP2C9*3 基因同型的患者完全禁用西泊尼莫德。此外,在开具处方前,应进行心电图检查、抗体状态评估、眼科评估、水痘疫苗接种情况和外周淋巴细胞计数,因为该药物的效果与剂量有关。因此,滴定过程从 0.25 毫克开始,直至 2 毫克。西泊尼莫德的药物治疗方案可靠地反映了药物遗传学在个性化医疗中的作用。
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[Siponimod (BAF312): General Characteristics and Clinical Implications of Pharmacogenomic Dosage in the Treatment of Active Secondary Progressive Multiple Sclerosis].

Siponimod is a selective immunosuppressive medication, developed as the first oral therapy for active secondary progressive multiple sclerosis. This medication acts by modulating the sphingosine 1 phosphate (S1P) receptor, as an antagonist of S1P1 and S1P5, thus preventing the egress of lymphocytes from lymph nodes and preventing inflammatory processes in the Central Nervous System that trigger demyelination. There is extensive scientific knowledge regarding the administration of the medication to patients, which will depend on their pharmacogenetic characteristics. Therefore, the FDA strongly recommends conducting a genotyping study of the enzyme that metabolizes siponimod, CYP2C9, whose genetic variants *2 and *3 classify patients as poor, extensive, or rapid metabolizers. Siponimod is completely contraindicated for patients who are homozygous for CYP2C9*3. Additionally, before prescribing it, an electrocardiogram, assessments of antibody status, ophthalmic evaluation, varicella vaccination status, and peripheral lymphocyte count should be conducted, as the medication's effect is dose-dependent. Therefore, a titration process is carried out starting from 0.25mg up to 2 mg. The pharmacotherapeutic protocol of siponimod is a reliable reflection of the utility of pharmacogenetics in personalized medicine.

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