The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women (KRF-LAC)

• ClinicalTrials.gov Identifier: NCT04285684
• Recruitment Status: Completed
• First Posted: February 26, 2020
• Results First Posted: December 13, 2021
• Last Update Posted: December 13, 2021
• Sponsor: The Ketamine Research Foundation
• Information provided by (Responsible Party): The Ketamine Research Foundation

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Conditions: Ketamine; Lactation
• Intervention: Drug: ketamine in lactation
• Enrollment: 4

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Ketamine During Lactation
Arm/Group Description	Participants received 2 ketamine administrations, 0.5mg/kg and 1.0mg/kg IM, at least 5 days apart.
Period Title: Overall Study
Started	4
Completed	4
Not Completed	0

Baseline Characteristics

Arm/Group Title		Ketamine During Lactation
Arm/Group Description		Participants received 2 ketamine administrations, 0.5mg/kg and 1.0mg/kg IM, at least 5 days apart.
Overall Number of Baseline Participants		4
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Between 21 and 45 years	Number Analyzed	4 participants
		4 100.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	Female	4 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	Hispanic or Latino	2 50.0%
	Not Hispanic or Latino	2 50.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 25.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	1 25.0%
	More than one race	0 0.0%
	Unknown or Not Reported	2 50.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	4 participants
		4
Postpartum with Established Lactation for a Minimum of 3 Months; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
		4 100.0%

Outcome Measures

1. Primary Outcome

Title	Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	51.2 (18.8)
6 Hours	22.6 (8.4)
9 Hours	10.6 (5.4)
12 Hours	4.5 (4.4)

2. Primary Outcome

Title	Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	125.0 (44.1)
6 Hours	48.2 (17.3)
9 Hours	21.6 (13.9)
12 Hours	18.5 (6.7)

3. Primary Outcome

Title	Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	42.6 (10.5)
6 Hours	28.6 (5.2)
9 Hours	18.8 (5.1)
12 Hours	8.7 (6.4)

4. Primary Outcome

Title	Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	92.7 (14.8)
6 Hours	62.4 (12.9)
9 Hours	37.3 (10.5)
12 Hours	32.3 (10.3)

5. Primary Outcome

Title	Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	.56 (.3)
6 Hours	.55 (.2)
9 Hours	.45 (.3)
12 Hours	.21 (.1)

6. Primary Outcome

Title	Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	2.0 (1.1)
6 Hours	1.9 (1.1)
9 Hours	1.4 (.7)
12 Hours	1.1 (.7)

7. Primary Outcome

Title	Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	29.9 (9.0)
6 Hours	28.3 (10.2)
9 Hours	25.6 (8.0)
12 Hours	17.5 (9.9)

8. Primary Outcome

Title	Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	3, 6, 9, and 12 hour collections

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: ng/mL
3 Hours	64.1 (21.1)
6 Hours	66.9 (13.1)
9 Hours	54.6 (11.2)
12 Hours	41.6 (9.8)

9. Primary Outcome

Title	Ketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	24 and 30 hour collections

Outcome Measure Data

Analysis Population Description

Based on the concentration of ketamine and its metabolites at 24 and 30 hours post ketamine administration in the first participant tested, breast milk was not collected for subsequent participants at these time frames.

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng/mL
24 Hours	4.9 [1] (NA)
30 Hours	6.4 [1] (NA)

[1]

Standard Deviation is not calculable for one participant.

10. Primary Outcome

Title	Norketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	24 and 30 hour collections

Outcome Measure Data

Analysis Population Description

Based on the concentration of ketamine and its metabolites at 24 and 30 hours post ketamine administration in the first participant tested, breast milk was not collected for subsequent participants at these time frames.

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng/mL
24 Hours	10.3 [1] (NA)
30 Hours	9.9 [1] (NA)

[1]

Standard Deviation is not calculable for one participant.

11. Primary Outcome

Title	Dehydronorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	24 and 30 hour collections

Outcome Measure Data

Analysis Population Description

Based on the concentration of ketamine and its metabolites at 24 and 30 hours post ketamine administration in the first participant tested, breast milk was not collected for subsequent participants at these time frames.

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng/mL
24 Hours	.3 [1] (NA)
30 Hours	.3 [1] (NA)

[1]

Standard Deviation is not calculable for one participant.

12. Primary Outcome

Title	Hydroxynorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine
Description	Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
Time Frame	24 and 30 hour collections

Outcome Measure Data

Analysis Population Description

Based on the concentration of ketamine and its metabolites at 24 and 30 hours post ketamine administration in the first participant tested, breast milk was not collected for subsequent participants at these time frames.

Arm/Group Title	Ketamine During Lactation
Arm/Group Description:	Participants received .5mg/kg and 1mg/kg IM ketamine, at least 5 days apart
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng/mL
24 Hours	30.5 [1] (NA)
30 Hours	13.9 [1] (NA)

[1]

Standard Deviation is not calculable for one participant.

Adverse Events

Time Frame	Adverse event data was collected continuously starting with the first ketamine administration, through the second ketamine administration (5-14 days following the first administration), and during a formal four week follow-up thereafter.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ketamine During Lactation
Arm/Group Description	Participants received 2 ketamine administrations, 0.5mg/kg and 1.0mg/kg IM, at least 5 days apart.
All-Cause Mortality
	Ketamine During Lactation
	Affected / at Risk (%)
Total	0/4 (0.00%)
Serious Adverse Events
	Ketamine During Lactation
	Affected / at Risk (%)
Total	0/4 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ketamine During Lactation
	Affected / at Risk (%)
Total	0/4 (0.00%)

Limitations and Caveats

After the collection of breast milk from the first subject, it was determined that 3 hour intervals up to 12 hours was a sufficient collection period for the study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Philip E Wolfson, MD
• Organization: Ketamine Research Foundation
• Phone: 415-550-1700
• EMail: ketamine.research@gmail.com

Publications:

Chang T, Glazko AJ. Biotransformation and disposition of ketamine. Int Anesthesiol Clin. 1974 Summer;12(2):157-77. doi: 10.1097/00004311-197412020-00018. No abstract available.

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.

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.

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.

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.

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.

• Responsible Party: The Ketamine Research Foundation
• ClinicalTrials.gov Identifier: NCT04285684
• Other Study ID Numbers: KetamineResearch
• First Submitted: February 24, 2020
• First Posted: February 26, 2020
• Results First Submitted: September 8, 2021
• Results First Posted: December 13, 2021
• Last Update Posted: December 13, 2021