Dipeptidylpeptidase-4抑制剂(gliptins):关注药物之间的相互作用。

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Scheen AJ

Dipeptidylpeptidase-4抑制剂(gliptins):关注药物之间的相互作用。

Pharmacokinet。2010年9月,49 (9):573 - 88。doi: 10.2165 / 11532980-000000000-00000。

PubMed ID

20690781 (在PubMed

]

文摘

患者2型糖尿病(T2DM)病人体内通常对待许多药物化合物和暴露于高危险的药物之间的相互作用。实际上,联合血糖控制通常需要各种降糖代理,和推荐的全球方法减少总体心血管风险通常意味着政府的几个保护化合物,包括β-还原酶抑制剂(他汀类药物),抗高血压化合物和抗血小板药物。新化合物开发改善glucose-inducedβ细胞分泌和血糖控制,没有诱导低血糖和体重增加,患者2型糖尿病。Dipeptidylpeptidase-4 (DPP-4)抑制剂新型降糖药物,这可能会被用来作为单一疗法或结合其他抗糖尿病的化合物,二甲双胍,thiazolidinediones甚至磺酰脲类药物。Sitagliptin, vildagliptin saxagliptin已经在市场上,作为单一代理商或与二甲双胍固定剂量组合配方。其他化合物,如alogliptin linagliptin,后期发展阶段。本文总结了可用的药物之间的相互作用在文献中报道的数据对这些五DDP-4抑制剂:sitagliptin, vildagliptin, saxagliptin, alogliptin linagliptin。之间可能的药代动力学干扰一直在调查这些化合物和各种药物,这被选中,因为还有其他降糖药物的(二甲双胍、格列本脲(优降糖)、吡格列酮/罗格列酮)可能规定结合DPP-4抑制剂,其他药物目前用于患者2型糖尿病(他汀类药物、抗高血压代理),化合物已知干扰细胞色素P450 (CYP)系统(酮康唑、地尔硫卓、利福平(利福平))或22运输(ciclosporin),或者代理一个狭窄的治疗安全窗口(华法林,地高辛)。一般来说,几乎没有药物之间的相互作用或只有轻微的药物之间的相互作用已报告DPP-4抑制剂与这些药物。gliptins不明显修改其他测试药物的药动学特征和接触,和其他药物不会显著改变gliptins或接触这些的药动学特征。 The only exception concerns saxagliptin, which is metabolized to an active metabolite by CYP3A4/5. Therefore, exposure to saxagliptin and its primary metabolite may be significantly modified when saxagliptin is coadministered with specific strong inhibitors (ketoconazole, diltiazem) or inducers (rifampicin) of CYP3A4/5 isoforms. The absence of significant drug-drug interactions could be explained by the favourable pharmacokinetic characteristics of DPP-4 inhibitors, which are not inducers or inhibitors of CYP isoforms and are not bound to plasma proteins to a great extent. Therefore, according to these pharmacokinetic findings, which were generally obtained in healthy young male subjects, no dosage adjustment is recommended when gliptins are combined with other pharmacological agents in patients with T2DM, with the exception of a reduction in the daily dosage of saxagliptin when this drug is used in association with a strong inhibitor of CYP3A4/A5. It is worth noting, however, that a reduction in the dose of sulfonylureas is usually recommended when a DPP-4 inhibitor is added, because of a pharmacodynamic interaction (rather than a pharmacokinetic interaction) between the sulfonylurea and the DPP-4 inhibitor, which may result in a higher risk of hypoglycaemia. Otherwise, any gliptin may be combined with metformin or a thiazolidinedione (pioglitazone, rosiglitazone), leading to a significant improvement in glycaemic control without an increased risk of hypoglycaemia or any other adverse event in patients with T2DM. Finally, the absence of drug-drug interactions in clinical trials in healthy subjects requires further evidence from large-scale studies, including typical subjects with T2DM - in particular, multimorbid and geriatric patients receiving polypharmacy.

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药物酶

药物	酶	类	生物	药理作用	行动
Saxagliptin	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节
Saxagliptin	细胞色素P450 3 a5	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
Saxagliptin	耐多药resistance-associated蛋白1	蛋白质	人类	未知的	底物	细节