Drug Concentrations in Breast Milk and Prediction of Blood Levels of the Breastfed Infants

Study Overview
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Brief Summary
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There is a significant lack of information on drug secretion into milk and infant exposure. As a first step to address this issue, the investigators examine milk concentrations of selected drugs prescribed to breastfeeding women, which lack milk excretion data. Milk data will be analyzed using population pharmacokinetic approaches, when possible, and acquired data of drug concentration profiles in milk will be combined with infant physiologically-based pharmacokinetic (PBPK) models to predict infant exposure levels.

Detailed Description
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In this study the investigators measure drug concentrations in breast milk (and optional blood) samples collected through sparse and flexible sampling strategy mitigating intense approaches of conventional PK study. Whenever possible, population PK method is used to characterize milk concentration profiles of the selected drugs. The obtained data is further processed through a PBPK model of infant to predict infant drug exposure levels. The study also includes an optional pharmacogenetic part. This will allow the investigators to understand how variations in genetic composition plays role in breaking down drugs and how it affects the drug transfer into breast milk. This study is conducted at three sites: Hospital for Sick Children (leading site), CHU Sainte Justine Hospital, Montreal (Study Lab: for drug measurement), and University of Waterloo (Modelling Core: to create computer model).

Official Title
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Drugs in Breast Milk

Conditions
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Breast Feeding

Intervention / Treatment
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* Drug: either of Atenolol, Bupropion, Brivaracetam, Escitalopram, Fluconazole, Lacosamide, Lamotrigine, Levetiracetam, Methotrexate or Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for breastfeeding women Age of 18 years or older Lactating women taking at least one of the study target drugs per Standard of Care Obtained informed consent Ability to communicate in English Exclusion Criteria for breastfeeding women Any concomitant medication Known pregnancy during PK sampling Inclusion criteria for their infant Older than 1 week Healthy Exclusion criteria for their infant Concomitant medical treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breastfeeding women<br>Either of the following drugs at steady state (Atenolol, Bupropion, Brivaracetam, Escitalopram, Fluconazole, Lacosamide, Lamotrigine, Levetiracetam, Methotrexate or Ezetimibe). | Drug: either of Atenolol, Bupropion, Brivaracetam, Escitalopram, Fluconazole, Lacosamide, Lamotrigine, Levetiracetam, Methotrexate or Ezetimibe<br>* This is a cohort study of pharmacokinetics of drugs in milk. Participants in the group are those breastfeeding women on the listed drugs at steady state, who are prescribed these drugs for clinical reasons outside this study framework.<br>* Other names: Typical brand names include, but not limited to: Tenoretic, Wellbutrin, Zyban, Briviact, Cipralex, Lexapro, Diflucan, Vimpat, Lamictal, Keppra, Trexall, Xatmep, Ezetrol, Nexlizet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| concentrations of target drugs in breast milk | using assays of drug concentrations validated in human milk as a matrix | an average of 1 year |