Bioanalysis, Drug Metabolism and New Drug Discovery

患有难治性双相抑郁症（BP）和诊断为复杂区域性疼痛综合征（CRPS）的无反应性慢性疼痛的患者对氯胺酮治疗有反应。CRPS患者接受为期五天的药物输注治疗，75%的患者疼痛缓解，67%的患者在单次剂量后血压缓解。正在进行的研究的目的是确定为什么有些患者有反应而有些没有反应的原因，能够在治疗开始前确定有反应的患者，并进行个体化治疗以增加反应。氯胺酮在CRPS和BP患者中的初始药代动力学和药效学研究已经完成。数据表明氯胺酮的治疗活性部分是由于羟基诺氯胺酮和脱氢诺氯胺酮，并且已经研究了这些化合物的药理活性。此外，代谢组学研究已经确定，BP患者对氯胺酮治疗的反应和不反应与线粒体功能有关。这一关系正在调查中。

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.