Reduction in elevated serum cholesterol concentrations is important in the management of individuals at risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and thrombotic stroke. Although HMGCoA reductase inhibitors (“statins”) are frequently used for this purpose, a significant proportion of patients remain at increased residual risk of ASCVD as they do not adequately address some of the associated co-morbidities such as diabetes and fatty liver disease. A double-blind, randomized, placebo-controlled, dose ranging study was carried out that compared three doses of berberine ursodeoxycholate (BUDCA) to placebo in a cohort of subjects with a history of hypercholesterolemia and serum LDL cholesterol levels above 2.59 mmol/L (> 99.9 mg/dL). BUDCA was administered in two divided doses each day for 28 days. The primary endpoints of the study were safety and tolerability of this new compound, as well as its effect in lowering serum lipid and lipoprotein concentrations. A total of 50 subjects were enrolled into three dose cohorts in this study. BUDCA was generally well tolerated, even at doses of 2000 mg per day (the highest dose group); there were no significant adverse effects reported and this highest dose was associated with significant reductions in LDL cholesterol. By day 28 and with the highest dose of BUDCA, there were significant reductions in the serum concentrations of total cholesterol by 8.2% (P = 0.0004) and LDL cholesterol by 10.4% (P = 0.0006), but no significant changes in triglyceride and HDL cholesterol concentrations. BUDCA is a new single molecular entity that has a significant but modest effect in safely lowering serum LDL-cholesterol concentrations in individuals with a history of hypercholesterolemia. It has a potential use for treating hypercholesterolemia in individuals who cannot take statins, and possibly as adjunctive to other agents, such as ezetimibe or bempedoic acid. The study was registered on Clinicaltrials.gov ( NCT03381287 ).

中文翻译：

---

HTD1801（熊去氧胆酸小檗碱，BUDCA）在高脂血症患者中的药代动力学和药效学

降低升高的血清胆固醇浓度对于管理有动脉粥样硬化性心血管疾病 (ASCVD) 风险的个体很重要，例如心肌梗塞和血栓性中风。尽管 HMGCoA 还原酶抑制剂（“他汀类药物”）经常用于此目的，但很大一部分患者仍处于 ASCVD 残余风险增加的状态，因为它们没有充分解决一些相关的合并症，如糖尿病和脂肪肝。进行了一项双盲、随机、安慰剂对照的剂量范围研究，该研究在一组有高胆固醇血症史且血清 LDL 胆固醇水平高于 2.59 mmol/L 的受试者中比较了三种剂量的熊去氧胆酸小檗碱 (BUDCA) 与安慰剂。 > 99.9 毫克/分升）。BUDCA 每天分两次给药，共 28 天。该研究的主要终点是这种新化合物的安全性和耐受性，以及它在降低血清脂质和脂蛋白浓度方面的作用。在这项研究中，共有 50 名受试者被纳入三个剂量组。BUDCA 通常耐受性良好，即使剂量为每天 2000 毫克（最高剂量组）；没有报告显着的不良反应，这个最高剂量与 LDL 胆固醇的显着降低有关。到第 28 天，使用最高剂量的 BUDCA，血清总胆固醇浓度显着降低 8.2% (P = 0.0004)，LDL 胆固醇浓度显着降低 10.4% (P = 0.0006)，但甘油三酯和 HDL 没有显着变化胆固醇浓度。BUDCA 是一种新的单分子实体，在安全地降低有高胆固醇血症病史的个体的血清 LDL-胆固醇浓度方面具有显着但适度的作用。它具有治疗不能服用他汀类药物的个体的高胆固醇血症的潜在用途，并且可能作为其他药物（如依折麦布或 bempedoic 酸）的辅助治疗。该研究已在 Clinicaltrials.gov (NCT03381287) 上注册。