The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women: Quantification of Ketamine and Metabolites

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.

Keywords: Ketamine; lactation; pharmacokinetics; postpartum depression; women’s health.