Vanadium treatment of type 2 diabetes: A view to the future
Vanadium treatment of type 2 diabetes: A view to the future
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DOI：
10.1016/j.jinorgbio.2008.12.003
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发表时间：
2009-04-01
影响因子：
3.9
通讯作者：
Orvig, Chris
中科院分区：
文献类型：
--
作者：
Thompson, Katherine H.;Lichter, Jay;Orvig, Chris
3-羟基-2-甲基-4-吡喃酮和2-乙基3-羟基-4-吡喃酮（分别为麦芽酚和乙基麦芽酚）已被证明特别适合氧钒吨的配体，适合糖尿病的潜在胰岛素增强剂。双(麦芽糖)氧钒(IV) (BMOV) 和乙基麦芽酚类似物双(乙基麦芽糖)氧钒(IV) (BEOV) 都具有前药用途所需的中间稳定性，并经过了广泛的安全性和有效性临床测试。药代动力学评估表明生物分布模式与相当快速的解离和摄取一致，与血清转铁蛋白结合进行全身循环并转运至组织，并优先在骨中摄取。这些双配体氧钒(IV) (VOL2) 化合物在生物利用度和药效方面比无机硫酸氧钒具有明显的优势。 BEOV现已完成I期临床试验，并已进入II期临床试验。在 I 期试验中，非糖尿病志愿者口服 10 mg 至 90 mg BEOV 的一系列剂量，没有产生任何不良反应，所有生化参数均保持在正常范围内。在 IIa 期试验中，BEOV (AKP-020)。对于 7 名 2 型糖尿病受试者，每日 20 毫克，口服 28 粒粘土，可降低空腹血糖、血糖和 %HbA1c；与两个安慰剂对照中观察到的糖尿病症状恶化相比，口服葡萄糖耐量测试的反应有所改善。 (C) 2009 Elsevier Inc. 保留所有权利。
3-Hydroxy-2-methyl-4-pryone and 2-ethyl 3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable a ligands for vanadyl tons, fit potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pie-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL2) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a ran-e of doses horn 10 mg, to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects, all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020). 20 mg, daily for 28 clays, per os, in seven type 2 diabetic Subjects, was associated with reductions in fasting blood and glucose and %HbA1c; improved responses to oral glucose tolerance testing, versus, the observed worsening of diabetic symptoms in the two placebo controls. (C) 2009 Elsevier Inc. All rights reserved.