PARENTERAL FORMULATION FOR CARBAMAZEPINE

卡马西平肠胃外制剂

• 批准号: 3504485
• 负责人: KERRY S ESTES
• 金额: $ 4.99万
• 依托单位: PHARMOS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1991-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3504485
• 关键词: anticonvulsants; carbamazepine; drug adverse effect; drug design /synthesis /production; epilepsy; intravenous administration; laboratory mouse; water solution

DESCRIPTION: (Adapted from Applicant's Abstract) The favorable efficacy, toxicity and adverse side-effect profiles of carbamazepine (CBZ) contribute to its widespread and increasing use to control seizure in the epileptic patient. However, in cases when oral drug treatment is not feasible, no parenteral formulation is available for CBZ. Currently epileptic patients who are unable to maintain oral CBZ must be treated with other anticonvulsants formulated for parenteral administration. This multiple drug approach often leads to unpredictable seizure control and increased drug toxicity in chronically CBZ treated patients. Our preliminary studies showed first that aqueous solutions of CBZ can be given intravenously (i.v.). Second, anticonvulsant activity of CBZ is unaltered in the mouse MES (maximal electroconvulsant shock) model when given in the aqueous formulation. Third, the i.v. total daily dose of CBZ projected to maintain seizure control can be formulated in a reasonable volume. This approach to parenteral formulation of CBZ is based on using a water soluble excipient which is known to form an inclusion complex with lipophilic drugs. The excipient has a favorable toxicity profile for i.v. dosing and the solutions are stable to heat sterilization. The proposed studies examine the feasibility of developing a parenteral formulation of CBZ based on this patented inclusion complex technology. Studies will explore: formulation stability, compatibility with other i.v. fluids, venous irritation, toxicity profiles and manufacturing reproducability. Successful development of a CBZ formulation for i.v. administration would benefit the epileptic patient who is unable to maintain oral CBZ therapy.

说明：（改编自申请人摘要）有利的功效， 卡马西平（CBZ）的毒性和不良副作用特征有助于 其广泛和越来越多地用于控制癫痫患者的发作， 病人 然而，在口服药物治疗不可行的情况下， CBZ的胃肠外制剂可用。 目前癫痫患者 不能维持口服CBZ的患者必须接受其他治疗 用于肠胃外给药的抗惊厥药。 这种多 药物方法往往导致不可预测的癫痫控制和增加 慢性CBZ治疗患者的药物毒性。 我们的初步研究 首次证明CBZ的水溶液可以静脉注射 （静脉注射）。第二，CBZ的抗惊厥活性在小鼠中没有改变 MES（最大电惊厥休克）模型，当在水溶液中给药时 公式化。 第三，静脉注射CBZ的每日总剂量预计将维持 癫痫控制可以配制成合理的体积。 这种方法来 CBZ的肠胃外制剂基于使用水溶性赋形剂 已知其与亲脂性药物形成包合复合物。 的 赋形剂对于静脉内给药具有有利的毒性特征， 溶液对热灭菌稳定。 拟议的研究审查了开发胃肠外制剂的可行性。 CBZ的配方基于这一专利的包合物技术。 研究将探索：制剂稳定性、与其他i.v. 液体、静脉刺激、毒性特征和制造 再现性 成功开发用于i.v. 给药将有益于不能 维持口服CBZ治疗。