safinamide的药代学和药效学,neuroprotectant和抗帕金森病的抗惊厥的活动。

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Marzo,木豆Bo L,蒙蒂数控,Crivelli F,伊斯玛仪派,Caccia C, C均,Fariello RG

safinamide的药代学和药效学,neuroprotectant和抗帕金森病的抗惊厥的活动。

药物杂志》2004年7月,50 (1):77 - 85。

PubMed ID

15082032 (在PubMed

]

文摘

目的:介绍了药物动力学和药效学,monoamino氧化酶的B型(缺氧)的抑制,在口头管理safinamide男性健康的志愿者,在实验中起到新模型有很强的抗惊厥的和antiparkinson活动。方法:四个临床试验的剂量范围25 - 10000 microg /公斤进行描述药物动力学、药效学和safinamide耐受性,管理在稳态单或重复剂量方案,包括食品相互作用试验。上述试验后进行了伦理委员会的批准和签名同意书的志愿者。单剂量试验的血液抽样涵盖了24 h-period药效学试验,48 h-period药代动力学试验。对于稳态pre-dose样本重复剂量方案是画在前六天学习,而曲线探讨了第七研究天,延长血液采样后48 h-period最后剂量。Safinamide水平确定在等离子体非常敏感和特定LC-MS-MS方法,量化的下限0.5 ng / ml的等离子体。药代动力学与non-compartmental方法进行了分析,在一个案例中,也与two-compartmental方法。单胺氧化酶A和B两种类型的活动(是和缺氧)决定在等离子体在不同的时间(缺氧)和相关safinamide水平,或尿(是)。结果:safinamide证明是线性药物动力学和比例与注射剂量有关。safinamide的吸收与血浆浓度峰值迅速从2到4 h。食品长期利率和safinamide并不影响吸收的程度。 In repeat dose regimen once daily, the steady state was reached on the 5th study day with a marginal accumulation factor of 1.5-1.7. The drug was cleared with a t(1/2) of about 22 h. Safinamide reversibly inhibited MAO-B enzyme. Full inhibition was observed with single doses >/= 600 microg/kg, and a relevant, dose dependent, progressive inhibition was encountered with doses starting from 25 microg/kg. Even at the highest single dose of 10 mg/kg no evidence of MAO-A inhibition was observed. CONCLUSION: Enteral absorption of the drug is linear and proportional to the doses administered. The drug is cleared from the body with a t(1/2) of approximately equal to 22 h, without producing any clinically relevant accumulation at steady state. The MAO-B inhibitory activity, without affecting MAO-A, is useful to prevent a dopamine bioinactivation in patients suffering from Parkinson's disease. Safinamide tolerability in the four clinical trials proved to be good.

DrugBank数据引用了这篇文章

药物

Safinamide

药物靶点

药物	目标	类	生物	药理作用	行动
Safinamide	胺氧化酶(flavin-containing) B	蛋白质	人类	是的	拮抗剂	细节

药物酶

药物	酶	类	生物	药理作用	行动
Safinamide	细胞色素P450 2 c19	蛋白质	人类	未知的	抑制剂	细节