The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ketamine, Lactation

Intervention / Treatment
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* Drug: ketamine in lactation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ketamine, lactation<br>Lactating women--4 subjects, 2 dosage format: ketamine 0;5mg/kg and 1.0mg/kg IM at least 5 days apart. | Drug: ketamine in lactation<br>* 2 dose IM by weight and assessing concentrations of ketamine in expressed milk at intervals<br>* Other names: Assessing concentration of ketamine in breast milk at intervals;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine | 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 | 3, 6, 9, and 12 hour collections | 
| Ketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine | 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 | 24 and 30 hour collections | 
| Norketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine | 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 | 24 and 30 hour collections | 
| Dehydronorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine | 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 | 24 and 30 hour collections | 
| Hydroxynorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine | 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 | 24 and 30 hour collections | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketamine, lactation, postpartum depression, breastfeeding, infant exposure