Bioanalysis, Drug Metabolism and New Drug Discovery

患有难治性双相抑郁症（BP）和诊断为复杂性局部疼痛综合征（CRPS）的无反应慢性疼痛的患者对氯胺酮治疗有反应。 CRPS患者接受了为期五天的药物输注治疗，75%的患者在单次给药后疼痛缓解，67%的BP有反应。正在进行的研究的目的是确定一些患者应答而另一些患者不应答的原因，以便能够在治疗开始前确定应答者，并个性化治疗以增加应答。 已完成氯胺酮在CRPS和BP患者中的这些初始药代动力学和药效学研究。 数据表明，氯胺酮的治疗活性部分归因于羟基去甲氯胺酮和脱氢去甲氯胺酮，并且已研究了化合物的药理学活性。 此外，代谢组学研究已经确定BP患者对氯胺酮治疗的应答和无应答与线粒体功能有关。 这种关系正在调查中。

In patients suffering from treatment-resistant bipolar depression (BP) and with unresponsive chronic pain that is diagnosed as Complex Regional Pain Syndrome (CRPS)have responded to treatment with ketamine. The CRPS patients were treated with a five-day infusion of the drug produced pain relief in 75% of the patients and 67% of the BP responded after a single dose. The objective of the ongoing study is to identify the reasons why some patients respond and other do not, to be able to identify the responders before treatment begins and to individualize treatment to increase response. These initial pharmacokinetic and pharmacodynamic studies of ketamine in CRPS and BP patients are completed. The data indicates that the therapeutic activity of ketamine is due, in part, to hydroxynorketamine and dehydronorketamine and the pharmacological activities of the compounds have been investigated. In addition, metabolomic studies have determined that response and non-response to treatment with ketamine in BP patients is related to mitochodrial function. This relationship is under investigation.