Comparing the Effect of Sodium valproate with Lithium carbonate on Suicidal Ideation of Patients with Bipolar Disorder in Manic Phase with Mediation of Interoception

开始日期2024-10-22

申办/合作机构

Mashhad University of Medical Sciences

IRCT20130313012810N38 / CompletedIIT

Comparative bioequivalence study of the Lithium carbonate 300-mg Tablets manufactured by Vana Darou Gostar Pharmaceutical Company

开始日期2024-09-19

申办/合作机构-

NCT06184581 / Recruiting临床4期IIT

Lithium Versus Lamotrigine in Bipolar Disorder, Type II - a Single Blinded Randomized Controlled Trial (the LiLa-Bipolar RCT)

The investigators want in a 6-month randomized controlled trial (RCT) to compare effects of lithium versus lamotrigine on mood stabilization and other critical patient outcomes in patients with BDII.

开始日期2024-05-08

申办/合作机构-

100 项与碳酸锂相关的临床结果

登录后查看更多信息

100 项与碳酸锂相关的转化医学

登录后查看更多信息

100 项与碳酸锂相关的专利（医药）

登录后查看更多信息

2,488

项与碳酸锂相关的文献（医药）

2025-01-01·EXPERIMENTAL NEUROLOGY

Modeling of TDP-43 proteinopathy by chronic oxidative stress identifies rapamycin as beneficial in ALS patient-derived 2D and 3D iPSC models

Article

作者: Battaglia, Cristina ; Ratti, Antonia ; Venturin, Marco ; Bossolasco, Patrizia ; Invernizzi, Sabrina ; Sorce, Marta Nice ; Colombrita, Claudia ; Lattuada, Chiara ; Silani, Vincenzo ; Casiraghi, Valeria ; Santangelo, Serena

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized neuropathologically by TDP-43 proteinopathy with loss of TDP-43 nuclear splicing activity and formation of cytoplasmic TDP-43 aggregates. The lack of suitable experimental models of TDP-43 proteinopathy has hampered the discovery of effective therapies. We already showed that chronic and mild oxidative insult by sodium arsenite (ARS) triggered TDP-43 cytoplasmic aggregation and stress granules (SGs) formation in ALS patient-derived fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs). However, whether this insult induces a reduction of TDP-43 splicing activity in the nucleus, thus recapitulating both gain and loss of function pathomechanisms, still remains to be determined. In this study we first showed that chronic ARS in human neuroblastoma cells triggered TDP-43 cytoplasmic mislocalization, SGs formation and defective splicing of TDP-43 target genes UNC13A and POLDIP3 as functional readouts of TDP-43 proteinopathy. Additionally, a dysregulation of autophagy and senescence markers was observed in this condition. In a preliminary drug screening approach with autophagy-promoting drugs, namely rapamycin, lithium carbonate and metformin, only rapamycin prevented ARS-induced loss of TDP-43 splicing activity. We then demonstrated that, in addition to TDP-43 cytoplasmic aggregation, chronic ARS triggered TDP-43 loss of splicing activity also in ALS patient-derived primary fibroblasts and iPSC-MNs and that rapamycin was beneficial to reduce these TDP-43 pathological features. By switching to a neuro-glial 3D in vitro model, we observed that treatment of ALS iPSC-brain organoids with chronic ARS also induced a defective TDP-43 splicing activity which was prevented by rapamycin. Collectively, we established different human cell models of TDP-43 proteinopathy which recapitulate TDP-43 gain and loss of function, prevented by rapamycin administration. Human neuroblastoma cells and patient-derived fibroblasts and 2D- and 3D-iPSC models exposed to chronic oxidative stress represent therefore suitable in vitro platforms for future drug screening approaches in ALS.

2024-09-02·Drug and chemical toxicology

Hesperidin via maintenance of mitochondrial function and antioxidant activity protects lithium toxicity in rat heart isolated mitochondria

Article

作者: Salimi, Ahmad ; Shabani, Mohammad ; Bayrami, Deniz ; Jamali, Zhaleh

Lithium is commonly used in the treatment of bipolar disorders (BD) and consumer electronics. It has been reported that lithium exposure is associated with mitochondrial dysfunction and oxidative stress in isolated cardiac mitochondria. Mitochondrial protection has a key role in myocardial tissue homeostasis, cardiomyocyte survival and inhibition of cardiotoxicity. Hesperidin as a flavanone and cardioprotective agent has shown high potential in antioxidant activity and restoration of mitochondrial dysfunction in different models. Therefore, we aimed to evaluate the ameliorative effects of hesperidin against lithium-induced mitochondrial toxicity in rat cardiac mitochondria. Isolated mitochondria were classified into six groups; control, lithium carbonate (125 µM), three groups of lithium + hesperidin-treated received lithium (125 µM) and hesperidin with various concentrations (10, 50, and 100 µM) and hesperidin (100 µM). Succinate dehydrogenases (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial glutathione (GSH) and lipid peroxidation (LPO) were measured. The mitochondria received lithium showed a significant reduction of SDH activity, MMP collapse, mitochondrial swelling, induction of ROS formation and lipid peroxidation. However, we observed that the administration of hesperidin (50 and 100 µM) resulted in the increase of SDH activity, improved MMP collapse, mitochondrial swelling, and reduced ROS formation and lipid peroxidation. Also, there were no obvious changes in cardiac mitochondria received of hesperidin. These findings suggest that hesperidin could reduce lithium-induced mitochondrial dysfunction through antioxidant activities in cardiac mitochondria, may be beneficial for prevention and treatment of lithium toxicities, either as a drug to treat BD or as an environmental pollutant.

2024-09-01·Oxford Medical Case Reports

A case of acute lithium poisoning and hypermagnesemia involving advanced colon cancer-induced colonic obstruction

Article

作者: Nishikawa, Masashi ; Kagaya, Takashi ; Komura, Takuya ; Onishi, Ichiro ; Takayama, Hideo ; Kawane, Taro ; Omi, Wataru ; Yamashita, Taro ; Matsuo, Toshiki ; Sakajiri, Kenichi ; Kimura, Makiko ; Sakagami, Satoru ; Kitagawa, Kiyoki

Abstract:

An 83-year-old woman presented with disturbance of consciousness and hand tremor. She had taken lithium carbonate 300 mg/day for bipolar disorder and magnesium oxide 660 mg/day for constipation. Blood tests revealed lithium poisoning, hypermagnesemia and acute kidney injury. Computed tomography showed colonic obstruction caused by cancer of the descending colon. In the outpatient section, her blood pressure decreased to 89/54 mmHg, and her heart rate dropped to 40 bpm. We considered that the obstructive ileus induced intravascular dehydration, which led to toxic serum concentrations of lithium and magnesium, triggering the emergence of severe arrythmia induced by sinus dysfunction. The patient was treated with fluid resuscitation and hemodialysis, followed by endoscopic stent replacement for the descending colon cancer obstruction. These treatments improved her general condition and alleviated the lithium poisoning, hypermagnesemia and colonic obstruction. Such a case is considered extremely rare.

项与碳酸锂相关的新闻（医药）

2024-11-19

·Business Wire

Alzamend Neuro Announces Full Data Set from its Nonclinical Study: Comparing Brain and Plasma Lithium Exposures between AL001 and Lithium Carbonate in Alzheimer’s Transgenic Mice

ATLANTA--( BUSINESS WIRE )-- Alzamend Neuro, Inc. (Nasdaq: ALZN) (“ Alzamend ”), a clinical-stage biopharmaceutical company focused on developing novel products for the treatment of Alzheimer’s disease (“ Alzheimer’s ”), bipolar disorder (“ BD ”), major depressive disorder (“ MDD ”) and post-traumatic stress disorder (“ PTSD ”), today announced that it has finished analyzing the final full data set from a nonclinical study comparing brain and plasma lithium exposures between AL001 and lithium carbonate in Alzheimer’s transgenic mice. The study was conducted at the University of South Florida and the bioanalytical procedures for determination of lithium concentration in the brain and plasma samples were conducted under good laboratory practice standards by Sannova Analytical LLC. The study involved administering AL001, a good manufacturing practices-quality active pharmaceutical ingredient (“ API ”) to 5XFAD mice, a recognized model for Alzheimer’s research, to compare its effects against lithium carbonate, a U.S. Food and Drug Administration (“ FDA ”) approved and marketed API. Mice received either high or low doses scaled to humans of both AL001 and lithium carbonate over a 14-day period to observe pharmacokinetic steady-state drug conditions. On the 15th day, the mice were analyzed to assess how the treatments affected lithium concentrations in different brain regions and in their plasma. Key Findings : No Undue Adverse Effects: Both treatments had no negative impact on the mice's body weight or clinical signs during the treatment period. Reduced Systemic Exposure: AL001 showed lower plasma lithium levels than lithium carbonate, reducing the risk of adverse systemic effects, suggesting an expansion for safety of lithium’s therapeutic index. Enhanced Brain Penetration: AL001 showed consistently higher lithium concentrations in brain tissues, particularly at lower doses, compared to lithium carbonate. Targeted Brain Structures: The study found that different brain regions absorb and retain lithium differently. This means treatments can potentially be tailored to target specific brain areas, allowing for more precise treatment of various brain-related conditions when applied in human studies. Clinical Implications: These results highlight the potential clinical advantages of AL001 for conditions like Alzheimer’s, BD, MDD and PTSD at low doses. By reducing the systemic burden, AL001 could lessen the risk of side effects such as thyroid and kidney complications often associated with extant lithium therapies. This positions AL001 as a promising candidate for safer long-term treatment options, without the need for routine blood lithium monitoring. This innovation is specifically designed to address the needs of fragile populations, such as elderly and Alzheimer’s patients, by offering a potentially more efficient and safer alternative to existing treatments. “This is a major step towards potentially providing an important treatment innovation for the 43+ million Americans afflicted with Alzheimer’s, BD, MDD and PTSD. These results demonstrated the potential of AL001 to enhance brain-specific lithium delivery while minimizing systemic exposure in an Alzheimer’s disease mouse model, guiding development of enhanced lithium effectiveness and safety in human diseases,” said Stephan Jackman, Chief Executive Officer of Alzamend. “We appreciate the extraordinary efforts of our colleagues and partners. We look forward to further evaluating AL001 in five ‘Lithium in Brain’ Phase II clinical trials in healthy subjects and patients diagnosed with mild to moderate Alzheimer’s, BD, MDD and PTSD, in partnership with Massachusetts General Hospital at the dosing level observed to be appropriate in this nonclinical study.” About Alzamend Neuro Alzamend is an early clinical-stage biopharmaceutical company focused on developing novel products for the treatment of Alzheimer’s, BD, MDD and PTSD. Our mission is to rapidly develop and market safe and effective treatments. Our current pipeline consists of two novel therapeutic drug candidates, AL001 - a patented ionic cocrystal technology delivering lithium via a therapeutic combination of lithium, salicylate, and L-proline, and AL002 - a patented method using a mutant-peptide sensitized cell as a cell-based therapeutic biologic vaccine that seeks to restore the ability of a patient’s immunological system to combat Alzheimer’s. Both of our product candidates are licensed from the University of South Florida Research Foundation, Inc. pursuant to royalty-bearing exclusive worldwide licenses. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “believes,” “plans,” “anticipates,” “projects,” “estimates,” “expects,” “intends,” “strategy,” “future,” “opportunity,” “may,” “will,” “should,” “could,” “potential,” or similar expressions. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties. Forward-looking statements speak only as of the date they are made, and Alzamend undertakes no obligation to update any of them publicly in light of new information or future events. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors. More information, including potential risk factors, that could affect Alzamend’s business and financial results are included in Alzamend’s filings with the U.S. Securities and Exchange Commission. All filings are available at www.sec.gov and on Alzamend’s website at www.Alzamend.com .

疫苗临床2期临床结果

2024-10-16

·贵州医科大学

国际首次！贵州医科大学谭俊教授团队发现全新小分子USP11抑制剂用于阿尔茨海默病治疗

阿尔茨海默症（Alzheimer’s disease，AD）是一种进行性神经退行性疾病，主要病理学特征由细胞外淀粉样蛋白-β（Amyloid β, Aβ）沉积形成的老年斑（Senile plaques, SP）和神经元细胞内高度磷酸化tau聚集形成的神经纤维缠结（Neurofibrillary tangles, NFTs）构成。这两种病理蛋白在脑内的异常积累与突触功能障碍、神经元死亡和AD认知缺陷密切相关。因此靶向上述蛋白及其病理机制开发疾病修饰（disease-modifying）治疗药物一直是AD领域的研究热点。 2022年发表的Cell文章发现，X染色体相关的泛素特异性肽酶11（Ubiquitin-specific protease 11，USP11）的高表达会促进 tau 的去泛素化和稳定性，从而阻止 tau 蛋白的正常清除，加速 tau 的病理性聚集，导致 AD 小鼠的认知功能障碍。USP11基因敲除后，能够显著改善AD小鼠的tau病变和认知功能的受损。因此抑制USP11介导的tau去泛素化进而改善AD病理有望为AD治疗提供全新的策略。目前已知的 USP11 小分子抑制剂主要是米托蒽醌，主要用于治疗急性髓系白血病等多种恶性肿瘤。但由于水溶性差、长期使用有较为严重的药物不良反应，尤其是在老年、合并症多的患者中出现特别的心脏毒性，因此难于在临床上推广应用于老年AD患者。为此，安全有效的新型小分子USP11抑制剂的研发仍然亟待解决。历经四年，贵州医科大学谭俊教授团队与大连医科大学附属第一医院李崧研究员合作通过大量的筛选优化得到了全新结构的小分子USP11选择性抑制剂IsoLiPro（尼布林），并利用多种转基因AD动物模型反复进行实验，在国际上首次明确了其临床前抗AD的作用。这一研究结果，不仅有助于我们全面了解AD的发病机制，同时也为AD新药开发开辟了全新的方向，并对其它以USP11为靶点的临床疾病的治疗产生了重要影响。据了解，全新小分子USP11抑制剂已经由谭俊教授团队成立的新药研发公司——安域生物科技（杭州）有限公司进行产业化的开发应用，预计在2024年底或2025年初在中国开展临床试验。 2024年10月，贵州医科大学/浙大城市学院谭俊教授团队和大连医科大学附属第一医院李崧研究员合作在EMBO Molecular Medicine杂志在线发表了题为“Targeting USP11 regulation improvesneuropathologies and cognition in Alzheimer transgenic mice”的研究文章。该研究在国际上首次明确了小分子USP11抑制剂能够通过增加tau蛋白泛素化，促进其降解清除，从而改善AD病理和认知损害，发挥抗AD作用。这一研究发现为开发新的AD治疗策略提供了全新的靶标。同时，全方位探索了尼布林作为新药在长期应用中的毒副作用以及药代学特征，结果表明，尼布林具有低的毒性且具有较好的动力学特征，为后续的临床研究提供基础。（拓展阅读：谭俊课题组往期进展，详见“逻辑神经科学”报道（点击阅读）：CMLS︱贵州医科大学谭俊团队合作揭示淀粉样前体蛋白N端通过调控胞外tau蛋白跨膜转运加剧阿尔茨海默病tau病理的机制；Transl Psychiatry︱浙江大学谭俊团队合作发现淀粉样前体蛋白促进SARS-CoV-2入侵并加剧阿尔茨海默病风险） 1、尼布林的合成与表征图1 Synthesis and characterization of IsoLiPro. 将等摩尔量的异丁酸锂（LiIB）和L-脯氨酸（Pro）在正丁醇中加热回流，搅拌约3 h后自然冷却结晶，收集产生的晶体并对其进行了结构解析和性质表征（图1）。XRPD、1H-NMR、FT-IR等多种分析技术均证明，尼布林是一种结构稳定的配位化合物。 2、IsoLiPro 在体外和体内均可显著降低 USP11 蛋白水平为了进一步探索尼布林对USP11的抑制效果，课题组在SH-SY5Y细胞和HEK293细胞中筛选多种小分子药物和尼布林对细胞中USP11的抑制作用，结果表明尼布林对USP11 的抑制效果最明显，且能够时间和剂量依赖性降低SH-SY5Y细胞的USP11表达水平，同时这一抑制作用具有USP11选择性。在体内研究中，9.5月龄的3xTg-AD小鼠灌胃给药尼布林4月后，尼布林对USP11蛋白水平也有相同的抑制作用，其海马和皮层区域的USP11表达水平均显著降低（图2）。图2 IsoLiPro markedly decreases USP11 protein level inSH-SY5Y cells and the mice brain 3、IsoLiPro 显着增加 HEK293-hTau 细胞中的 tau 泛素化水平为了进一步探讨尼布林加速tau蛋白清除的机制，课题组通过免疫沉淀（IP）结合液相色谱-质谱联用技术（LC-MS/MS）对tau蛋白的泛素化进行了分析。实验结果表明，尼布林处理HEK293-hTau细胞后，tau蛋白的K48泛素化水平显著升高（图3）。这一结果进一步提示，尼布林能够通过降低USP11表达，抑制tau蛋白的去泛素化，从而增加其降解清除，最终降低总tau和磷酸化tau水平。图3 IsoLiPro alters tau ubiquitination levels inHEK293-hTau cells. 4、尼布林显著缓解AD 转基因小鼠模型大脑中的病理变化，并改善认知功能障碍在上述细胞水平实验的基础上，课题组进一步利用3xTg-AD和5xFAD两种转基因AD动物模型，评估了尼布林对tau病理的影响。研究人员发现，9.5月龄的3xTg-AD小鼠和10周龄的5xFAD小鼠口服尼布林后，大脑中的总tau蛋白和磷酸化tau蛋白（p-tau181, p-tau202/205和p-tau396）显著降低。同时，尼布林还能显著降低 5xFAD 小鼠脑组织海马区的Iba1和 GFAP 水平，表明尼布林能够改善胶质细胞激活和神经炎症反应。意外的是，尼布林给药后不仅显著改善 tau 病理和神经炎症，还能显著降低脑内Aβ水平和斑块沉积，这一结果可能与尼布林通过抑制USP11表达，参与BACE1泛素化和降解以及 Li 对 GSK-3β 激酶的活性降低有关。除了tau病理、神经炎症和Aβ 病理斑块外，课题组的研究结果还发现尼布林长期给药后能够增加突触标志物SYN-1和PSD95蛋白的表达，并显著提高神经元树突棘密度和数量，表明尼布林能够显著改善AD模型动物的神经突触可塑性（图4）。Morris水迷宫和Y迷宫实验结果表明，与对照组相比，经过尼布林治疗的实验动物展示出更好的行为表现。此外，除了验证了尼布林对缓解AD病变作用及机制进行研究外，还对其毒性以及药代等试验结果进行了评估。结果表明，尼布林在长期给药过程中未发现明显的毒性反应。与碳酸锂相比，到达大脑中的锂浓度更高，具有较好的药代学特征，。这些均为尼布林的临床研究提供更进一步的基础。图4 IsoLiPro ameliorates synaptic plasticity deficits andspatial memory impairment 图5 尼布林抗AD作用机制示意图文章结论与讨论，启发与展望本研究首次在体内和体外模型中证实了尼布林能够有效降低USP11蛋白水平。机制研究表明，这一作用主要通过调节USP11的蛋白质降解途径实现，而非直接影响其酶活性。通过降低USP11的蛋白水平，尼布林能够增强tau蛋白的泛素化，从而加速其降解，改善AD转基因动物模型中的病理特征。这些结果揭示了USP11作为阿尔茨海默病（AD）治疗潜在靶点的重要性，并为通过抑制USP11蛋白水平治疗AD提供了新思路（图5）。然而，本研究也存在一些值得进一步探索的问题。首先，虽然本研究表明尼布林能够调控USP11蛋白降解，但要准确反映其在体内的作用机制，还需要进一步定量分析尼布林在大脑中的分布和浓度。通过明确其剂量-反应关系，可以更加精准地评估尼布林的有效剂量范围，优化治疗方案。此外，未来的研究应进一步聚焦尼布林与USP11在体内尤其是大脑中的直接相互作用，以揭示更为精准的分子机制。结合这些信息，我们的研究将能够为尼布林作为AD治疗药物提供更强的基础理论支持，并有助于开发相关疾病中基于USP11的靶向治疗策略。原文链接：https://www-embopress-org.libproxy1.nus.edu.sg/doi/full/10.1038/s44321-024-00146-7 本文共同通讯作者：谭俊博士，贵州医科大学特聘教授；李崧博士，大连医科大学附属第一医院神经疾病研究所研究员。本文第一作者为贵州医科大学郭义博士。来源：逻辑神经科学作者：郭义李崧编辑：李菡逸一审：李牧二审：钱禾三审：陈颖往期回顾 RECENTLY RELEASED 贵州医科大学2025年硕士研究生招生章程及专业目录贵州医科大学2025届毕业生冬季校园招聘会邀请函探索校园 | 从临床医学院“协和楼”，探寻中式建筑之美贵州医科大学版权所有期待投稿合作邮箱：gmctougao@163.com

临床结果临床研究

2024-08-28

·Business Wire

Release of Negotiated Prices Under Inflation Reduction Act Reveals that BRENZAVVY® (bexagliflozin) Remains the Lowest Priced SGLT2 Inhibitor

MARLBOROUGH, Mass.--( BUSINESS WIRE )-- TheracosBio today announced that, in the wake of the federal government release of negotiated prices under the Medicare Drug Price Negotiation Program, BRENZAVVY® (bexagliflozin) remains the lowest priced sodium-glucose cotransporter 2 (SGLT2) as compared to the Negotiated Monthly List Price, also referred to as the Maximum Fair Price, for other drugs in the SGLT2 class. “ While we salute the work that the federal government is doing to reduce the cost of pharmaceuticals, including important therapies for people on Medicare with type 2 diabetes, the sad fact remains that, even at sharply reduced prices for the leading brands in the class, the majority of people who might benefit from the addition of an SGLT2 will remain financially unable to start and stay on therapy ,” said Brian Connelly, President and CEO of TheracosBio. “ TheracosBio, since its founding, has been committed to addressing such financial barriers traditionally associated with pharmaceutical therapy in common, chronic diseases like type 2 diabetes ,” Mr. Connelly added. In the United States, BRENZAVVY is sold at a low cash-pay price, usually $50 or less, through a network of online and independent pharmacies. As patients prescribed BRENZAVVY are often uninsured, underinsured, or on Medicare, this lowest-in-class price point makes SGLT2 therapy affordable for a larger number of people who might otherwise not be able to start and stay on therapy. For healthcare professionals, BRENZAVVY can easily be prescribed without insurance plan hurdles that the SGLT2 class traditionally faces, such as prior authorizations. BRENZAVVY is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. BRENZAVVY is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. Phase 3 clinical studies have shown BRENZAVVY significantly reduces hemoglobin A1c and fasting blood sugar after 24 weeks, either as a monotherapy, in combination with metformin, or as an add-on to standard-of-care treatment consisting of a variety of regimens, including metformin, sulfonylureas, insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors or combinations of these drugs. BRENZAVVY is available as 20 mg oral tablets recommended to be taken once daily, in the morning with or without food. BRENZAVVY is contraindicated in patients who are hypersensitive to bexagliflozin or any other ingredient in the BRENZAVVY tablet. The most common side effects of taking BRENZAVVY include female genital mycotic infections, urinary tract infections, and changes in urination, but more serious side effects are possible (see below, Important Safety Information about BRENZAVVY). BRENZAVVY treatment can be initiated in adults with type 2 diabetes with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 mL/min/1.73 m 2 . Patients with eGFR between 30 and 59 mL/min/1.73 m 2 are said to be in stage 3 chronic kidney disease. BRENZAVVY was the first SGLT2 inhibitor shown in a randomized, controlled clinical trial to be effective for glycemic control in adults with type 2 diabetes and stage 3 (3a + 3b) chronic kidney disease. To learn more about BRENZAVVY and for full prescribing information visit https://www.brenzavvy.com . To report suspected adverse reactions, contact TheracosBio at 1-855-BRENZAVVY (1-855-273-6928) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Important Safety Information about BRENZAVVY Limitation of Use: BRENZAVVY (bexagliflozin) is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. Contraindications BRENZAVVY is contraindicated in patients with hypersensitivity to bexagliflozin or any excipient in BRENZAVVY. Anaphylaxis and angioedema have been reported with sodium-glucose co-transporter 2 (SGLT2) inhibitors. Warnings and Precautions Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis BRENZAVVY increases the risk of life-threatening ketoacidosis in patients with type 1 diabetes. Type 2 diabetes and pancreatic disorders are also risk factors for ketoacidosis and fatal events of ketoacidosis have been reported in patients with type 2 diabetes using SGLT2 inhibitors. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms of diabetic ketoacidosis are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Assess patients who present with signs and symptoms of metabolic ketoacidosis, regardless of blood glucose levels. If suspected, discontinue BRENZAVVY, treat promptly and monitor for resolution before restarting. Consider ketone monitoring in patients with type 1 diabetes mellitus as well as in others at risk for ketoacidosis. Withhold BRENZAVVY in clinical situations known to predispose to ketoacidosis and resume when clinically stable. Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue BRENZAVVY and seek medical attention immediately if signs and symptoms occur. Lower Limb Amputation Lower limb amputations have been observed in patients treated with BRENZAVVY in a study of patients with type 2 diabetes who had either established cardiovascular disease (CVD) or were at risk for CVD. Of the 23 BRENZAVVY-treated patients who had amputations, 15 were amputations of the toe and midfoot and 8 were amputations above and below the knee. Some patients had multiple amputations. Lower limb infections, gangrene, ischemia, and osteomyelitis were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy. Before initiating BRENZAVVY, consider factors in the patient’s history that may predispose to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients receiving BRENZAVVY about the importance of routine preventative foot care and monitor for signs and symptoms of diabetic foot infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment. Volume Depletion BRENZAVVY can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors. Before initiating, assess volume status and renal function in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, patients with low systolic blood pressure, or patients on loop diuretics. In patients with volume depletion, correct this condition. After initiating, monitor for signs and symptoms of volume depletion and renal function. Urosepsis and Pyelonephritis Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been identified in patients receiving SGLT2 inhibitors, including BRENZAVVY. Treatment with BRENZAVVY increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat them promptly. Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin and insulin secretagogues (e.g., sulfonylureas) are known to cause hypoglycemia. BRENZAVVY may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with BRENZAVVY. Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) Serious, life-threatening cases requiring urgent surgical intervention have been identified in postmarketing surveillance in both males and females with diabetes mellitus receiving SGLT2 inhibitors. Serious outcomes have included hospitalization, multiple surgeries, and death. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal areas, along with fever or malaise. If suspected, start treatment, and discontinue BRENZAVVY. Genital Mycotic Infections BRENZAVVY increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately. MOST COMMON ADVERSE REACTIONS (>5%): Female genital mycotic infections, urinary tract infection and increased urination. USE IN SPECIFIC POPULATIONS Pregnancy: BRENZAVVY is not recommended during the second and third trimesters. Lactation: BRENZAVVY is not recommended when breastfeeding. Geriatric patients: There is a higher incidence of adverse reactions related to volume depletion. Renal Impairment: There is a higher incidence of adverse reactions related to reduced renal function. Hepatic Impairment: BRENZAVVY is not recommended for patients with severe hepatic impairment. DRUG INTERACTIONS: Inducers of UGT1A9 could result in more rapid clearance of BRENZAVVY by metabolism. Doses of insulin and sulfonylureas may need to be reduced to offset the action of BRENZAVVY. The safety of BRENZAVVY is compromised when it is coupled with insulin or an insulin secretagogue (sulfonylureas and meglitinides – the latter rarely used in the US). Lithium carbonate is used as a mood stabilizer in bipolar disorder. Lithium ions might be preferentially (compared to sodium ions) taken up with glucose in the kidney. Empirical evidence has shown that lithium levels can be lower when SGLT2 inhibitors are administered. SGLT2 inhibitors produce pronounced glucosuria, which makes urine testing for glucose diagnostically useless. Measurements of 1,5 anhydroglucitol are also compromised. For additional important safety information about BRENZAVVY, please see the full Prescribing Information . About TheracosBio TheracosBio develops novel therapeutics for diseases with significant societal impact. The mission of TheracosBio is to expand access to new medications for patients with common diseases.

临床3期临床结果上市批准

100 项与碳酸锂相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D00801	碳酸锂	N05AN01	DB14509

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
躁郁症1型	美国	Hikma Pharmaceuticals USA, Inc.	1982-01-29
躁郁症	美国	Pfizer Inc.	1970-04-06
躁郁症	美国	Solvay Pharmaceuticals, Inc.	1970-04-06
分裂情感性障碍	美国	Solvay Pharmaceuticals, Inc.	1970-04-06
分裂情感性障碍	美国	Pfizer Inc.	1970-04-06

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
克莱恩-莱文综合征	临床前	欧盟	Laboratoires Delbert SAS	2023-08-16

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02918097 (CTgov)	临床4期	躁郁症	78	Lithium Carbonate+Risperidone+Nortriptyline+Sertraline	積顧壓製衊築壓願襯選(鬱壓衊壓餘襯艱衊遞網) = 顧築淵夢簾窪構淵壓餘蓋鏇夢齋構淵鑰簾糧窪 (襯齋鑰鬱遞鑰憲鬱醖糧, 築積顧窪齋齋鏇獵構鏇 ~ 壓製憲鹹鬱艱選餘積獵) 更多	-	2020-10-14
NCT01820624 (Pubmed) 人工标引	临床1期	急性髓性白血病	9	lithium carbonate+tretinoin	鬱鹹廠鏇衊遞鹽夢蓋鬱(壓淵夢鏇簾淵齋窪願鬱) = 襯範夢餘憲壓簾構齋衊餘築淵顧廠艱鏇繭衊餘 (鑰鏇鬱繭夢鬱廠廠築鏇 )	不佳	2020-03-10
NCT01553916 (CTgov)	临床1/2期	小细胞肺癌	19	Prophylactic cranial irradiation+Lithium Carbonate	餘襯淵憲鑰廠壓餘鏇製(艱餘築觸齋淵艱蓋願製) = 構夢淵製選醖夢憲鬱築積願膚遞膚鬱積積壓廠 (襯艱鬱齋衊蓋淵壓餘鏇, 醖憲鬱構顧窪構鏇觸淵 ~ 艱構襯壓廠餘願蓋構網) 更多	-	2017-11-08
NCT00501540 (CTgov)	临床2期	神经内分泌肿瘤	15	Lithium Carbonate	獵願獵鹽鹽襯簾獵範觸(膚憲獵鹹艱襯壓衊鹹遞) = 選窪觸築願構構鬱蓋鬱願齋製鑰選鬱鑰鑰憲鬱 (範壓構膚簾鑰積觸廠鹹, 構夢憲顧選繭鑰繭廠艱 ~ 餘蓋構齋憲鑰窪夢膚夢) 更多	-	2017-05-03
NCT00408681 (GVHD, CTgov)	N/A	复发性急性髓细胞白血病 \| 复发性边缘区淋巴瘤 \| 妊娠滋养细胞疾病 ... 更多	20	laboratory biomarker analysis+lithium carbonate	觸醖醖築獵壓網壓齋獵(鬱淵淵憲醖鏇蓋觸淵壓) = 鑰願範鏇遞願廠選築願憲壓廠糧構獵範衊鑰鑰 (壓鹹憲夢衊鬱鑰遞憲餘, 壓網壓範廠膚製醖鏇糧 ~ 艱窪齋築淵淵糧觸繭憲)	-	2017-01-20
NCT00582712 (CTgov)	临床2期	甲状腺髓样癌	5	Lithium carbonate	艱構構餘簾醖壓壓膚觸(獵簾繭積築壓範糧齋廠) = 鹹艱廠蓋夢鹽膚製襯獵網廠糧願簾構齋築鏇積 (蓋鏇襯構遞鏇願顧獵齋, 憲積製選遞壓遞廠糧蓋 ~ 鹹夢築築遞憲齋範壓鑰) 更多	-	2016-12-12
NCT00240110 (CTgov)	临床1/2期	可卡因相关疾病 \| 躁郁症	152	Lithium Carbonate+Placebo (Lithium Carbonate Add on Placebo)	遞鏇簾鹽齋鑰鏇蓋製衊(築鬱鏇膚蓋鬱簾製顧選) = 繭廠鏇窪鬱廠憲構餘築獵積選製齋糧艱壓範網 (蓋鏇壓淵築鹽窪蓋繭網, 艱觸鬱範遞網醖齋鹽顧 ~ 願廠鹹廠餘願淵蓋衊繭) 更多	-	2016-10-17
NCT00240110 (CTgov)	临床1/2期	可卡因相关疾病 \| 躁郁症	152	Lithium Carbonate+Valproate (Lithium Carbonate Add on Valproate)	遞鏇簾鹽齋鑰鏇蓋製衊(築鬱鏇膚蓋鬱簾製顧選) = 積觸鏇構鬱網齋鑰鑰蓋獵積選製齋糧艱壓範網 (蓋鏇壓淵築鹽窪蓋繭網, 鏇餘遞網膚遞顧艱範蓋 ~ 鹽獵獵壓網窪窪窪簾網) 更多	-	2016-10-17
NCT00750061 (CTgov)	临床2期	脊髓损伤	40	Placebo (Placebo)	齋製蓋鏇觸簾壓鏇壓簾(餘築簾觸網鑰艱壓願艱) = 憲淵醖憲獵糧憲艱選網窪鹹醖淵糧選憲醖遞積 (齋鑰齋鏇繭製鹽膚餘襯, 鏇鏇鑰繭醖積選夢窪餘 ~ 遞艱鏇鑰糧繭繭壓鹹製) 更多	-	2015-05-04
NCT00750061 (CTgov)	临床2期	脊髓损伤	40	Lithium Carbonate (Lithium Carbonate)	齋製蓋鏇觸簾壓鏇壓簾(餘築簾觸網鑰艱壓願艱) = 選願夢夢願獵艱鏇網築窪鹹醖淵糧選憲醖遞積 (齋鑰齋鏇繭製鹽膚餘襯, 糧廠鹽選醖製鏇製積遞 ~ 蓋夢艱鏇遞艱憲淵鹹鏇) 更多	-	2015-05-04
NCT00667745 (LiTMUS, CTgov)	临床4期	躁郁症	283	Lithium Carbonate+risperidone+aripiprazole+divalproex+olanzapine+carbamazepine+Lithium+quetiapine+ziprasidone (OPT With Lithium)	願襯壓獵簾鹽簾鹹築鬱(壓艱觸餘鏇鑰製鏇糧範) = 夢獵襯膚選積顧鏇鑰顧獵鹹壓願獵築網範蓋糧 (遞鏇餘遞壓艱願衊獵鹹, 遞艱夢觸膚餘鑰廠獵襯 ~ 繭願網衊夢糧鬱醖積繭) 更多	-	2013-06-28
NCT00667745 (LiTMUS, CTgov)	临床4期	躁郁症	283	risperidone+aripiprazole+divalproex+olanzapine+carbamazepine+lithium+quetiapine+ziprasidone (OPT Without Lithium)	願襯壓獵簾鹽簾鹹築鬱(壓艱觸餘鏇鑰製鏇糧範) = 糧夢膚遞窪襯壓廠願遞獵鹹壓願獵築網範蓋糧 (遞鏇餘遞壓艱願衊獵鹹, 鬱繭醖觸遞觸顧廠醖顧 ~ 夢壓積醖鬱蓋齋鑰膚膚) 更多	-	2013-06-28
NCT00057681 (TEAM, CTgov)	临床3期	躁狂 \| 躁郁症	379	lithium (Randomized Medication - Lithium)	鹽廠積衊壓窪廠願鏇願(廠餘壓衊壓糧構獵積鏇) = 壓蓋淵壓鹽齋範夢蓋繭鹽蓋憲夢積觸鬱簾淵網 (窪壓醖艱選遞窪鹹夢鏇, 艱膚鑰網獵選壓選糧顧 ~ 選淵鹽鏇構膚夢築遞範) 更多	-	2013-03-27
NCT00057681 (TEAM, CTgov)	临床3期	躁狂 \| 躁郁症	379	Divalproex Sodium (Randomized Medication - Divalproex Sodium)	鹽廠積衊壓窪廠願鏇願(廠餘壓衊壓糧構獵積鏇) = 艱顧構築積窪糧壓積襯鹽蓋憲夢積觸鬱簾淵網 (窪壓醖艱選遞窪鹹夢鏇, 繭鬱鏇餘鏇築憲夢積製 ~ 淵衊築簾獵艱襯網壓觸) 更多	-	2013-03-27