Section of Preventive Medicine, Department of Cardiology, Rush University College of Medicine, Chicago, IL, USA; Radiant Research, 515 North Street, Chicago, IL 60610, USA.
J Clin Lipidol. 2007 Aug;1(4):271-9. doi: 10.1016/j.jacl.2007.07.005. Epub 2007 Jul 19.
AGI-1067 (succinobucol) is a phenolic derivative of probucol that inhibits the vascular oxidative-inflammatory cascade and is intended to have an improved clinical profile.
The Assessment of Lipoprotein Profiles (ALPS) study evaluated the effects of AGI-1067 on lipid, antioxidant, antiinflammatory and safety profiles in healthy subjects.
This was a double-blind, placebo-controlled, 12-week, multicenter trial. Eligible subjects, aged 18 to 65 years, had low-density lipoprotein cholesterol (LDL-C) ≤ 190 mg/dL, triglyceride (TG) ≤ 600 mg/dL and Framingham risk <10%. Subjects were randomized 1:1 to oral 300 mg AGI-1067 (n = 127) or matching placebo (n = 127) once daily.
AGI-1067 and placebo treatment had small changes (mean) in: LDL-C (+2.98 vs -1.52 mg/dL, respectively; P = 0.057), apolipoprotein B (+1.48 vs -1.91 mg/dL; P = 0.267), high-density lipoprotein cholesterol (HDL-C) [-3.69 vs -0.29 mg/dL; P < 0.001], and apolipoprotein (Apo) A-I (-10.43 vs -6.14 mg/dL; P = 0.021). Subjects with baseline LDL-C > 130 mg/dL showed the largest decreases in HDL-C and ApoA-I, while subjects with LDL-C ≤130 mg/dL had insignificant changes in both parameters. Changes in cholesteryl ester transfer protein mass were significantly correlated (P < 0.0001) with LDL-C changes, but not HDL-C. Paraoxonase activity increased with AGI-1067 vs little change in placebo (+1.78 vs +0.15 U/L, respectively; P = 0.077). HDL particles isolated from AGI-1067 treated subjects showed significant antioxidant potency vs HDL particles from placebo subjects (thiobarbituric acid reactive substances in a LDL oxidation assay decreased -25.88% vs +7.88, respectively; P = 0.011).
The ALPS study demonstrated that AGI-1067 had minor effects on LDL and HDL cholesterol. More dramatic effects were observed for HDL-associated paraoxonase and thiobarbituric acid reactive substances activity, suggesting that the antiatherosclerotic properties of AGI-1067 may involve an HDL antioxidant mechanism consistent with inhibition of the oxidative-inflammatory cascade, rather than involving a lipid regulating pathway.
AGI-1067（琥珀酸苏可布醇）是一种普罗布考的酚类衍生物，可抑制血管氧化炎症级联反应，旨在改善临床特征。
脂蛋白谱评估（ALPS）研究评估了 AGI-1067 对健康受试者的脂质、抗氧化剂、抗炎和安全性特征的影响。
这是一项双盲、安慰剂对照、为期 12 周、多中心试验。年龄在 18 至 65 岁之间、低密度脂蛋白胆固醇（LDL-C）≤190mg/dL、甘油三酯（TG）≤600mg/dL 和弗雷明汉风险<10%的合格受试者。受试者以 1:1 的比例随机接受口服 300mg AGI-1067（n=127）或匹配安慰剂（n=127），每日一次。
AGI-1067 和安慰剂治疗对 LDL-C（分别增加 2.98 与-1.52mg/dL；P=0.057）、载脂蛋白 B（分别增加 1.48 与-1.91mg/dL；P=0.267）、高密度脂蛋白胆固醇（HDL-C）（分别减少-3.69 与-0.29mg/dL；P<0.001）和载脂蛋白 A-I（分别减少 10.43 与-6.14mg/dL；P=0.021）有小的变化。基线 LDL-C>130mg/dL 的受试者 HDL-C 和 ApoA-I 下降最大，而 LDL-C≤130mg/dL 的受试者这两个参数变化不明显。胆固醇酯转移蛋白质量的变化与 LDL-C 的变化显著相关（P<0.0001），但与 HDL-C 无关。对氧磷酶活性随 AGI-1067 增加，而安慰剂变化不大（分别增加 1.78 与+0.15U/L；P=0.077）。与安慰剂受试者相比，接受 AGI-1067 治疗的受试者的 HDL 颗粒显示出显著的抗氧化能力（在 LDL 氧化测定中，硫代巴比妥酸反应物质减少-25.88%与+7.88%，分别；P=0.011）。
ALPS 研究表明，AGI-1067 对 LDL 和 HDL 胆固醇的影响较小。对于与 HDL 相关的对氧磷酶和硫代巴比妥酸反应物质活性，观察到更明显的影响，这表明 AGI-1067 的抗动脉粥样硬化特性可能涉及一种 HDL 抗氧化机制，与抑制氧化炎症级联反应一致，而不是涉及脂质调节途径。
