fingolimod的临床药物动力学。
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大卫橙汁,终于JM, Schmouder RL
fingolimod的临床药物动力学。
Pharmacokinet。2012年1月1日,51 (1):15-28。doi: 10.2165 / 11596550-000000000-00000。
- PubMed ID
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22149256 (在PubMed]
- 文摘
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Fingolimod (FTY720)鞘氨醇1-phosphate受体调制器,是第一个在一类新的治疗化合物和是第一个批准用于口服疗法治疗复发的多发性硬化症(MS)形式。Fingolimod是内生鞘氨醇的结构模拟和经历磷酸化Fingolimod磷酸盐、活动的一部分。Fingolimod目标女士通过对免疫系统的影响,从动物模型和证据表明它也可能在中枢神经系统的行为。III期研究中患者的复发缓和多发性,fingolimod已经证明疗效优于批准的一线治疗,肌肉interferon-beta-1a,以及安慰剂,福利扩展在临床和磁共振成像的措施。fingolimod的药代动力学资料和fingolimod磷酸盐在健康的志愿者都进行了广泛的调查研究中,肾移植受者(fingolimod最初的迹象在临床开发,但随后停止发展)和MS患者。结果从这些研究表明fingolimod有效吸收,与口服生物利用度> 90%,膳食摄入量及其吸收不受影响,因此可以不考虑。Fingolimod和磷酸Fingolimod半衰期6 - 9天,和稳态药物动力学是每日剂量的1 - 2个月后达到。fingolimod的长半衰期,连同其吸收缓慢,意味着fingolimod平浓度资料随着时间的每日一次给药。Fingolimod和磷酸Fingolimod dose-proportional暴露在单和multiple-dose研究一系列0.125 5毫克;因此,有一个可预测的剂量和系统性风险之间的关系。 Furthermore, fingolimod and fingolimod phosphate exhibit low to moderate intersubject pharmacokinetic variability. Fingolimod is extensively metabolized, with biotransformation occurring via three main pathways: (i) reversible phosphorylation to fingolimod phosphate; (ii) hydroxylation and oxidation to yield a series of inactive carboxylic acid metabolites; and (iii) formation of non-polar ceramides. Fingolimod is largely cleared through metabolism by cytochrome P450 (CYP) 4F2. Since few drugs are metabolized by CYP4F2, fingolimod would be expected to have a relatively low potential for drug-drug interactions. This is supported by data from in vitro studies indicating that fingolimod and fingolimod phosphate have little or no capacity to inhibit and no capacity to induce other major drug-metabolizing CYP enzymes at therapeutically relevant steady-state blood concentrations. Population pharmacokinetic evaluations indicate that CYP3A inhibitors and CYP3A inducers have no effect or only a weak effect on the pharmacokinetics of fingolimod and fingolimod phosphate. However, blood concentrations of fingolimod and fingolimod phosphate are increased moderately when fingolimod is coadministered with ketoconazole, an inhibitor of CYP4F2. The pharmacokinetics of fingolimod are unaffected by renal impairment or mild-to-moderate hepatic impairment. However, exposure to fingolimod is increased in patients with severe hepatic impairment. No clinically relevant effects of age, sex or ethnicity on the pharmacokinetics of fingolimod have been observed. Fingolimod is thus a promising new therapy for eligible patients with MS, with a predictable pharmacokinetic profile that allows effective once-daily oral dosing.
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- 药物
- 药物靶点
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药物 目标 类 生物 药理作用 行动 Fingolimod 鞘氨醇1-phosphate受体1 蛋白质 人类 是的调制器细节 Fingolimod 鞘氨醇1-phosphate受体3 蛋白质 人类 是的调制器细节 Fingolimod 鞘氨醇1-phosphate受体4 蛋白质 人类 未知的调制器细节 - 药物反应
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反应 细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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药物 交互 整合药物之间
在您的软件的交互Fingolimod 卡马西平 Fingolimod的血清浓度时可以减少与卡马西平相结合。 Fingolimod 酮康唑 Fingolimod的血清浓度时可以增加与酮康唑相结合。
