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

ABSTRACT

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
• postpartum depression
• pharmacokinetics
• women’s health

Author notes

The authors confirm that the Principal Investigator for this study is Philip E Wolfson MD, and that he had direct clinical responsibility for patients. All authors confirm the Originality of this text and this Research

Each of the authors state that there are no conflicts of interest and no relationships with commercial interests.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Written informed consent was obtained from all participants and the Informed Consent as approved by both the FDA and the IRB is appended.

Acknowledgments

The study was entirely funded by the non-profit Ketamine Research Foundation.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/02791072.2022.2101903

Additional information

Funding

This work was supported by the The Ketamine Research Foundation;