单一的药物动力学、药效学和耐受性增加剂量的dipeptidyl peptidase-4抑制剂alogliptin在健康男性受试者。

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卡温顿Christopher R P,达文波特M,斑点P, Mekki QA,呃,什么时候卡里姆

单一的药物动力学、药效学和耐受性增加剂量的dipeptidyl peptidase-4抑制剂alogliptin在健康男性受试者。

其他。2008年3月,30(3):513 - 27所示。doi: 10.1016 / j.clinthera.2008.03.005。

PubMed ID

18405789 (在PubMed

]

文摘

背景:Alogliptin是一种高度选择性dipeptidyl peptidase-4 (DPP-4)抑制剂在治疗2型糖尿病的发展。摘要目的:本研究以药物动力学的特征,进行药效学和耐受性单一口服剂量的alogliptin健康男性受试者。方法:这是一个随机、双盲、安慰剂对照研究中,健康,nonobese年龄在18岁至55岁之间的男性受试者被分配到1 6组:alogliptin 25岁,50岁,100,200,400,或800毫克。一个主题在每个组接受安慰剂。ascending-dose战略,分配每个队列中获得其剂量后回顾前面的队列的安全数据。血液和尿液收集超过72小时后剂量药代动力学分析和测定血浆DPP-4抑制和活跃glucagon-like肽1 (GLP-1)浓度。结果:36个科目每个队列(66)登记,完成了研究(29/36[81%]白;平均年龄26.6岁;平均体重76.0公斤)。Alogliptin迅速吸收(中值T (max), 1 - 2小时),慢慢消除(T(1/2), 12.4 - -21.4小时),主要通过尿排泄(平均分数从0到72小时尿液中药物剂量后,60% - -71%)。 C(max) and AUC(0-infinity) increased dose proportionally over the range from 25 to 100 mg. The metabolites M-I (N-demethylated) and M-II (N-acetylated) accounted for <2% and <6%, respectively, of alogliptin concentrations in plasma and urine. Across alogliptin doses, mean peak DPP-4 inhibition ranged from 93% to 99%, and mean inhibition at 24 hours after dosing ranged from 74% to 97%. Exposure to active GLP-1 was 2- to 4-fold greater for all alogliptin doses compared with placebo; no dose response was apparent. Hypoglycemia (asymptomatic) was reported in 5 subjects (11 receiving alogliptin 50 mg, 2 receiving alogliptin 200 mg, 1 receiving alogliptin 400 mg, 1 receiving placebo). Other adverse events were reported in 1 subject each: dizziness (alogliptin 100 mg), syncope (alogliptin 200 mg), constipation (alogliptin 200 mg), viral infection (alogliptin 400 mg), hot flush (placebo), and nausea (placebo). CONCLUSION: In these healthy male subjects, alogliptin at single doses up to 800 mg inhibited plasma DPP-4 activity, increased active GLP-1, and was generally well tolerated, with no dose-limiting toxicity.

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药物

Alogliptin