Wolfson Philip, Cole Rob, Lynch Kara, Yun Cassandra, Wallach Jason, Andries Julane, Whippo Melissa
The Ketamine Research Foundation, CA, USA.
J Psychoactive Drugs. 2023 Jul-Aug;55(3):354-358. doi: 10.1080/02791072.2022.2101903. Epub 2022 Jul 26.
Ketamine is a general anesthetic with over 50 years of safe administration that is in increasing use for psychiatric indications. This is evidenced by the recent FDA approval of intranasal esketamine (the S-enantiomer) for the treatment of depression. With respect to ketamine and lactation, incredibly there are no available data on the secretion of ketamine or its metabolites in human breast milk. This information is essential to guide the use of ketamine in breastfeeding women who suffer with postpartum emotional disorders, ongoing depression, PTSD, and more. To address this unmet need, we conducted a pharmacokinetic analysis of the presence of ketamine and several of its major metabolites (norketamine, dehydronorketamine, and hydroxynorketamine isomers) in four women receiving two different intramuscular doses of ketamine - 0.5 mg/kg and 1.0 mg/kg. Our results demonstrate low and rapidly declining levels of ketamine and metabolites in breast milk during the 12-hour post-dosing period. The mean relative infant dose (RID) obtained from AUC estimates for the 0.5 and 1.0 mg/kg doses were 0.650% and 0.766%, respectively. This provides the foundation for studying the use of ketamine during the post-partum period.
氯胺酮是一种有着50多年安全使用记录的全身麻醉剂，目前在精神科适应症方面的应用越来越广泛。美国食品药品监督管理局（FDA）最近批准鼻内用艾司氯胺酮（S-对映体）用于治疗抑郁症，这一现象就证明了这一点。令人难以置信的是，关于氯胺酮及其代谢产物在人母乳中的分泌情况，目前尚无可用数据。这些信息对于指导患有产后情绪障碍、持续性抑郁症、创伤后应激障碍等疾病的哺乳期妇女使用氯胺酮至关重要。为了满足这一未被满足的需求，我们对四名接受两种不同肌肉注射剂量氯胺酮（0.5毫克/千克和1.0毫克/千克）的女性进行了药代动力学分析，检测她们母乳中氯胺酮及其几种主要代谢产物（去甲氯胺酮、脱氢去甲氯胺酮和羟基去甲氯胺酮异构体）的存在情况。我们的结果表明，给药后12小时内，母乳中氯胺酮和代谢产物的水平较低且迅速下降。从0.5毫克/千克和1.0毫克/千克剂量的曲线下面积（AUC）估计值得出的平均相对婴儿剂量（RID）分别为0.650%和0.766%。这为研究产后期间氯胺酮的使用提供了依据。
