Clinical trial NCT04285684: The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women
Official title: The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women: Quantification of Ketamine and Metabolites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Ketamine
Lactation
Keywords: ketamine
lactation
postpartum depression
breastfeeding
infant exposure
Lead sponsor: The Ketamine Research Foundation
Sponsor class: OTHER
First posted: 2020-02-26
Enrollment: 4
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 4 subjects receiving 0.5mg/kg and 1.0mg/kg of ketamine at least 5 days apart with collection of breast milk by pumping at 3 hour intervals
Primary purpose: BASIC_SCIENCE

Brief summary: Quantification of Ketamine in Breast Milk at 3 hour Intervals up to 30 hours-- obtained from lactating women who receive 2 different Intramuscular injections of ketamine on two separate days at least 5 days apart.

Detailed description: Quantification of Ketamine in Breast Milk at 3 hour Intervals up to 30 hours-- obtained from lactating women who receive 2 different Intramuscular injections of ketamine on two separate days at least 5 days apart: 0.5mg/kg and 1.0mg kg.

Women are required to have been breast feeding for at least 3 months and be healthy and on no medications. Support is provided for the entire time at the site and for any at home pumping. During the period of ketamine's influence, subjects are reclining and with 2 Investigators. The initial subject's data will determine the length of time for pumping--most likely 12 hours as ketamine and the active principle metabolite have half-lives of less than 3 hours. Determination of concentration of ketamine in breast milk is being done at the UCSF Clinical lab with quantification of metabolites that are inactive as well. This research is of benefit by providing lactating women information on potential exposure of infants/children to ketamine. It will serve as a guide as KRF conducts research on postpartum depression and for women at large using ketamine for psychiatric indications.

Eligibility criteria: Inclusion Criteria:• Age 21-45

* Postpartum with established lactation for a minimum of 3 months.
* Ability to pump breast milk and to provide a reservoir for infant feeding prior to the study; or acceptance of bottle feeding by the infant.
* In good health-normal BP/P; afebrile-temp ascertained; review of systems by MD; absence of diagnosed illnesses.
* Not pregnant--Pregnancy tested for before each administration by urine assay.

Exclusion Criteria:• Hypertension with a BP greater than 145/90

* Subjects must be off all psychiatric medications specifically; medications and supplements, or evaluated by the PI for non-interference
* No alcohol or other substances such as marijuana for 72 hours or more.
* Weight \<50kg or \> 90kg.
* Pregnancy

Primary outcomes:
measure: Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
timeFrame: 3, 6, 9, and 12 hour collections
measure: Ketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
timeFrame: 24 and 30 hour collections
measure: Norketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
timeFrame: 24 and 30 hour collections
measure: Dehydronorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
timeFrame: 24 and 30 hour collections
measure: Hydroxynorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
timeFrame: 24 and 30 hour collections
Secondary outcomes:
Other outcomes:
Locations:
city: San Anselmo
country: United States
facility: Ketamine Research Foundation
state: California
Study officials:
affiliation: Ketamine Research Foundation
name: Philip E Wolfson, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Clements JA, Nimmo WS, Grant IS. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharm Sci. 1982 May;71(5):539-42. doi: 10.1002/jps.2600710516.
citation: Dore J, Turnipseed B, Dwyer S, Turnipseed A, Andries J, Ascani G, Monnette C, Huidekoper A, Strauss N, Wolfson P. Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy. J Psychoactive Drugs. 2019 Apr-Jun;51(2):189-198. doi: 10.1080/02791072.2019.1587556. Epub 2019 Mar 27.
citation: Little B, Chang T, Chucot L, Dill WA, Enrile LL, Glazko AJ, Jassani M, Kretchmer H, Sweet AY. Study of ketamine as an obstetric anesthetic agent. Am J Obstet Gynecol. 1972 May 15;113(2):247-60. doi: 10.1016/0002-9378(72)90774-0. No abstract available.
citation: Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.
citation: Weber F, Wulf H, Gruber M, Biallas R. S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children. Paediatr Anaesth. 2004 Dec;14(12):983-8. doi: 10.1111/j.1460-9592.2004.01358.x.