萨力多胺的临床药物动力学。

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科尔伯恩Teo SK,佤邦,Tracewell WG公司将雇员更多columbus方面,怪人KA,斯特灵DI, Jaworsky女士,Scheffler妈,托马斯•SD Laskin OL

萨力多胺的临床药物动力学。

43 Pharmacokinet。2004;(5): 311 - 27所示。doi: 10.2165 / 00003088-200443050-00004。

PubMed ID

15080764 (在PubMed

]

文摘

萨力多胺是一种外消旋谷氨酸导数在美国批准对结节性红斑红斑,麻风病的并发症。此外,它的使用在各种炎症和肿瘤情况正在调查中。萨力多胺之间的互换(R) - - - (S)对映体在等离子体与蛋白结合分别为55%和65%。超过90%的吸收药物是在48小时内尿液和粪便中排出。萨力多胺具有最低限度由肝脏代谢,但自发水解成许多肾排泄的产品。单剂量口服后萨力多胺200毫克(如美国表示支持胶囊配方)在健康的志愿者,吸收缓慢而广泛,导致峰值浓度(C (max)) 1 - 2 mg / L的管理3 - 4小时后,吸收滞后时间30分钟,总曝光(AUC(∞)) 18毫克。h / L,明显消除半衰期6小时和明显的系统性10 L / h的间隙。萨力多胺药物动力学是最好的描述单舱模型与一阶吸收和消除。因为低溶解度的药物在胃肠道,萨力多胺展品吸收药物动力学限速反应(“触发器”现象),其消除速率快于其吸收速率。明显的消除半衰期6小时因此代表吸收,而不是消除。 The 'true' apparent volume of distribution was estimated to be 16L by use of the faster elimination-rate half-life. Multiple doses of thalidomide 200 mg/day over 21 days cause no change in the pharmacokinetics, with a steady-state C(max) (C(ss)(max)) of 1.2 mg/L. Simulation of 400 and 800 mg/day also shows no accumulation, with C(ss)(max) of 3.5 and 6.0 mg/L, respectively. Multiple-dose studies in cancer patients show pharmacokinetics comparable with those in healthy populations at similar dosages. Thalidomide exhibits a dose-proportional increase in AUC at doses from 50 to 400 mg. Because of the low solubility of thalidomide, C(max) is less than proportional to dose, and t(max) is prolonged with increasing dose. Age, sex and smoking have no effect on the pharmacokinetics of thalidomide, and the effect of food is minimal. Thalidomide does not alter the pharmacokinetics of oral contraceptives, and is also unlikely to interact with warfarin and grapefruit juice. Since thalidomide is mainly hydrolysed and passively excreted, its pharmacokinetics are not expected to change in patients with impaired liver or kidney function.

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药物

萨力多胺