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: 2578786
• 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/2578786
• 关键词: anticonvulsants; carbamazepine; clinical research; combination chemotherapy; dopamine agonists; drug adverse effect; drug interactions; drug metabolism; drug screening /evaluation; human subject; human therapy evaluation; lithium; mental disorder chemotherapy; mood disorders; pharmacokinetics; psychopharmacology; psychotropic drugs; relapse /recurrence; valproate

In order to devise more effective and safe pharmacotherapies for patients with refractory mood disorder, a number of pharmacokinetic properties of several psychotropic drugs are being studied. Recently, our group reported carbamazepine, but not valproate therapy, decreased single point (150 mg dose) bupropion pharmacokinetics (maximal concentration and 24 hour area under the curve). Secondly, levels of hydroxybupropion, a major active metabolite, were increased in both carbamazepine and valproate, but a decrease in the bupropion/hydroxybupropion ratio was only present in the carbamazepine group. The clinical impact of this differential pharmacokinetic finding remains to be fully explored, but may be the reason that bupropion levels are essentially undetectable during carbamazepine treatment. A third group of studies currently under investigation are the single point pharmacokinetics of two new, recently FDA-approved, anticonvulsants -- gabapentin (Neurontin(R)) and lamotrigine (Lamictil(R)). As it is likely that these medications will be used in rational polypharmacy algorithms, we plan to conduct similar pharmacokinetic parameter studies of each anticonvulsant and determine whether significant pharmacokinetic drug interaction exists with lithium carbonate. Our preliminary data to date suggest that lithium levels are not affected by either of these compounds.

为了为患者设计更有效和安全的药物治疗 患有难治性情绪障碍，许多药代动力学特性 正在研究几种精神药物。 最近，我们的小组 据报道卡马西平（但不是丙戊酸疗法）降低了单点 （150 mg剂量）安非他酮药代动力学（最大浓度和24 曲线下的小时区域）。 其次，羟基抑制水平，一个 卡马西平和 丙丙酸酯，但安非他酮/羟基抑制率的降低为 仅存在于卡马西平小组中。 临床影响 差异药代动力学发现还有待探索，但 可能是安非他酮水平基本上无法检测到的原因 在卡马西平治疗期间。 目前正在研究的第三组研究是单一的 两种新的，最近由FDA批准的抗惊厥药的药代动力学 -Gabapentin（Neurontin（R））和Lamotrigine（Lamictil（r））。 是 这些药物可能会用于理性的多疗法 算法，我们计划进行类似的药代动力学参数研究 每种抗惊厥药，并确定是否有明显的药代动力学 药物相互作用与碳酸锂存在。 我们的初步数据 日期表明锂水平不受任何两者的影响 化合物。