dipeptidylpeptidase-4抑制剂的药物动力学。

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Scheen AJ

dipeptidylpeptidase-4抑制剂的药物动力学。

糖尿病ob金属底座。2010年8月,12 (8):648 - 58。doi: 10.1111 / j.1463-1326.2010.01212.x。

PubMed ID

20590741 (在PubMed

]

文摘

2型糖尿病(T2DM)病人体内胰岛素分泌缺陷相结合是一种复杂的疾病和胰岛素的行动。新化合物已经发展为提高glucose-induced胰岛素分泌和血糖控制,没有诱导低血糖和体重增加。Dipeptidylpeptidase-4 (DPP-4)抑制剂是新的口服降糖药物,所谓的肠促胰岛素增强剂,可以作为单一疗法或结合其他抗糖尿病的化合物。Sitagliptin, vildaglipin saxagliptin市场上已经在许多国家,作为单一代理商或与二甲双胍固定剂量组合配方。其他DPP-4抑制剂,如alogliptin linagliptin,目前在开发的后期阶段。本文总结和比较了主要药物动力学(PK)属性,也就是说,吸收、分布、代谢和消除,这五个DPP-4抑制剂。可用数据得到健康的年轻男性受试者在临床试验中表现,患者2型糖尿病,肾功能不全或肝损伤患者。PK特征通常是相似的在年轻的健康受试者和中年超重糖尿病患者。一起gliptins有良好的口腔生物利用度不明显受食物摄入量的影响。PK /药效学特征,充分延长半衰期和持续DPP-4酶失活,通常允许一个单一的管理每天口服2型糖尿病; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug-drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Sitagliptin	细胞色素P450 2 c8	蛋白质	人类	未知的	底物	细节
Sitagliptin	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节

药物转运蛋白

药物	转运体	类	生物	药理作用	行动
Sitagliptin	22 - 1	蛋白质	人类	未知的	底物	细节