Medications in Breast Milk: A Convenience Pharmacokinetic Study

Study Overview
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Brief Summary
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The benefits of breastfeeding and human milk consumption by infants has been clearly demonstrated. Benefits to the infant include reduction of infant and childhood diseases and allergies. Benefits to the woman include more rapid return to pre-pregnancy weight and reduced risk of health problems such as cardiovascular disease and diabetes in the future. Many women take medications as part of their standard of care and for multiple medical reasons in the postpartum period, when breastfeeding occurs. This creates a need for information about the transfer of drugs taken by a woman into breast milk, and ultimately, to the infant. Unfortunately, there are limited pharmacokinetic (PK) data on many of the medications commonly taken by lactating women. Additionally, there are little data on how the PK of drugs are impacted by lactation, and how this may vary from woman to woman or with time throughout lactation. Uptake of drugs into breast milk can vary due to a number of factors, including drug lipophilicity; molecular weight; drug half-life; active transport in breast epithelial cells; protein binding in milk and plasma; and lipid composition of breast milk. In silico and animal models can provide some information on transfer of drugs into breast milk, however, there are large gaps remaining in our knowledge of drug transfer into human milk. This information is crucial to better inform providers and patients about the transfer of those drugs to human breast milk. The purpose of this study is to characterize the PK of specific drugs of interest taken by lactating women as part of their standard of care. The drugs of interest (DOI) will be based on medical relevance and availability throughout the course of the study. The purpose of this study is to characterize the PK of medications taken by lactating women as part of their standard of care.

Detailed Description
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This observational, pragmatic PK study will enroll lactating women who are taking medications that were prescribed by their treating medical provider or as an over-the-counter medication. Study investigators will not be prescribing or recommending medication use as part of this study. Feasibility of the study is enhanced by a partnership with The Milk Bank, which will refer women identified as taking medications to study investigators. Subjects will also be recruited from Eskenazi Health and IU Health. Blood and breast milk samples will be collected from lactating women prior to administration of a dose of drug and at varying time points after dosing to characterize maternal and infant plasma PK and transfer of drug into breast milk. Another phase of the study will evaluate plasma concentrations of DOIs in breastfed infants whose mothers are already taking the medications. Infant blood samples will be obtained by heel stick or venipuncture from enrolled infants in order to determine the concentration of the drug in the infant's blood. The design of this study allows for the evaluation of the use of drugs in lactating women with minimal risk to participants. As blood draws and expressed milk samples are obtained often during clinical care or daily postpartum life, this study is not greater than minimal risk. Lactating women taking a DOI will have biospecimens collected from maternal breast milk and maternal blood. Breast milk will be collected from pumped or manually expressed samples.

Official Title
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Medications in Breast Milk: A Convenience Pharmacokinetic Study (The MedMilk Study)

Conditions
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Pregnancy Related

Intervention / Treatment
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* Drug: The MedMilk study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women who are lactating, or who are admitted and/or consented for cesarean delivery and planning to breastfeed postpartum, AND are receiving at least one DOI per standard of care from their provider or through self-care (for over-the-counter medications). Mothers who are at least 18 years of age and no more than 45 years of age Exclusion Criteria: Induced lactation Currently taking medication or supplements to increase milk production Diagnosis of any significant chronic medical condition including (but not limited to) hepatitis, HIV, heart failure, liver or renal failure, or malabsorption conditions (e.g. celiac disease or inflammatory bowel disease) known to alter PK of DOI, unless the DOI is the indicated treatment for that disease Alcohol use within 72 hours of study visit or planned PK blood draws Illicit substance, other than THC, use within 1 week of study visit or planned PK blood draws

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: The MedMilk study|This observational, pragmatic PK study will enroll lactating women who are taking medications that were prescribed by their treating medical provider or as an over-the-counter medication.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug concentration in maternal blood | Area under the plasma concentration versus time curve (AUC) | study duration, typically up to 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug concentrations in breast milk at steady state | Baseline and steady-state plasma concentrations of DOI in infants | study duration, typically up to 8 hours | 
| Relative infant dose- drug concentration in infant blood sample | calculation of relative infant dose | study duration, typically up to 8 hours |