{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:44:51Z","timestamp":1791474291454,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>The American Academy of Pediatrics and the World Health Organization recommend exclusive breastfeeding for the first 6 months of life due to extensive benefits for the maternal\u2013infant dyad. While over 90% of mothers initiate breastfeeding, continuation drops to 35% by 6 months, often due to concerns about medication safety. Clinicians often face decisions about medication use during lactation in the absence of robust data. Factors such as molecular weight (MW), lipid solubility, protein binding and a drug\u2019s acid\u2013base status are routinely stated as the determinants of drug passage into milk and used as \u201crules of thumb\u201d (e.g., MW &lt;500\u2009Da). However, these have not been rigorously examined for clinical applicability. This study investigates MW, protein binding, milk\u2010to\u2010plasma ratios (M\/P), and relative infant dose (RID) with the aim of assisting clinicians\u2019 estimation of medication safety during breastfeeding. Small\u2010molecule drugs with well\u2010documented M\/P were selected using predefined criteria. Physicochemical properties and active transporter status were compiled from multiple databases. Analyses investigated relationships between physicochemical properties, M\/P, and RID. A total of 94 drugs were included in the physicochemicalM\/P analyses, 91 for the M\/P\u2010RID analysis and 91 for the protein binding\u2010RID analysis. Our study highlights the complexities of predicting drug passage into breast milk, finding no straightforward MW cutoff for passage of small molecules. These findings challenge common assumptions and emphasize the importance of considering active transport and other physicochemical properties. While protein binding &gt;75% can serve as a preliminary guide, slow maternal drug clearance and active metabolites can decrease its utility.<\/jats:p>","DOI":"10.1002\/cpt.70021","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T06:15:07Z","timestamp":1755152107000},"page":"101-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Rules of Thumb for Estimating Drug Levels in Breast Milk: How Well Do They Work?"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3054-7726","authenticated-orcid":false,"given":"Juliya","family":"Gasparyan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Division of Clinical Pharmacology &amp; Toxicology The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5649-217X","authenticated-orcid":false,"given":"Philip O.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San Diego  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2137-8339","authenticated-orcid":false,"given":"Tamorah","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Pediatrics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-6376","authenticated-orcid":false,"given":"Cindy H. 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