PHARMACOKINETICS IN THE TREATMENT OF REFRACTORY MOOD DISORDERS

难治性心境障碍治疗中的药代动力学

• 批准号: 3759510
• 负责人: T KETTER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3759510
• 关键词: anticonvulsants; antidepressants; bipolar depression; bipolar depression manic phase; carbamazepine; combination chemotherapy; dopamine agonists; drug adverse effect; drug interactions; drug metabolism; generalized seizures; human subject; human therapy evaluation; liver metabolism; mental disorder chemotherapy; mood disorders; pharmacokinetics; psychopharmacology; psychotropic drugs; valproate

In order to devise more effective pharmacotherapies for patients with refractory mood disorders, we have begun studies of the clinical and pharmacokinetic effects of treatments with combinations of psychotropic agents. The aminoketone atypical antidepressant bupropion (BUP) is of particular interest, as it appears effective in refractory depression and may yield manic switches and rapid cycling less frequently than older antidepressant agents. However, seizures can occur during high dose BUP therapy. Combination of BUP with the mood stabilizing anticonvulsants carbamazepine (CBZ) or valproate (VPA) are strategies which could lessen the risks of both mania and seizures. Such therapies could be complicated by pharmacokinetic drug interactions, as CBZ induces hepatic metabolism of various medications, whereas valproate can inhibit hepatic metabolism. Preliminary data suggest that CBZ causes dramatic decreases in BUP levels an increases in levels of the metabolite hydroxybupropion (H-BUP), while VPA does not affect BUP levels and yields smaller increases in H-BUP. We plan to examine the relationships between such pharmacokinetic observations and clinical efficacy.

为了为患者设计更有效的药物治疗 难治性情绪障碍，我们已经开始研究临床和 治疗与精神疗法的混合物的药代动力学作用 代理商。 氨基酮非典型抗抑郁剂安非他酮（BUP）是 特别感兴趣，因为它在难治性抑郁症和 可能会产生躁狂开关和快速循环的频率 抗抑郁药。 但是，高剂量bup期间可能发生癫痫发作 治疗。 BUP与情绪稳定抗惊厥药的结合 卡马西平（CBZ）或丙戊酸（VPA）是可以减少的策略 躁狂和癫痫发作的风险。 这种疗法可能很复杂 通过药代动力学相互作用，CBZ诱导了肝代谢 各种药物，而丙戊酸可以抑制肝代谢。 初步数据表明，CBZ导致BUP水平急剧下降 代谢产物羟基抑制（H-BUP）的水平增加，而 VPA不会影响BUP水平，并且H-BUP的增加较小。 我们 计划检查此类药代动力学观察之间的关系 和临床功效。