{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:45:47Z","timestamp":1782456347093,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sirolimus is a mammalian target of rapamycin inhibitor that has been used in solid organ transplantation and is now increasingly being administrated to treat various manifestations of Tuberous Sclerosis (TSC). Lack of data regarding its safety during breastfeeding has led to its contraindication by pediatric and breastfeeding guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Levels of sirolimus were evaluated in breast milk samples collected during 24\u00a0h on the 10th and 15th day postpartum, by a lactating TSC patient chronically medicated with 4\u00a0mg of sirolimus per day. Controls were healthy lactating women. Serum levels of sirolimus were also evaluated on the TSC patient on the 10th day postpartum (at the beginning of breast milk collection) but not in the newborn, since the patient was advised not to breastfeed. An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC\u2013MS\/MS) method, including solid\u2013liquid extraction (SLE) for sample preparation, was optimized and validated for the quantitation of sirolimus in breast milk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After optimization, the SLE-UHPLC-MS\/MS method allowed the detection of 100\u00a0pg sirolimus per mL\n                      <jats:sup>-1<\/jats:sup>\n                      of breast milk. Sirolimus was detected in all breast milk samples from the TSC patient, ranging from 173 to 492\u00a0pg. mL\n                      <jats:sup>-1<\/jats:sup>\n                      . However, its concentration was more than 10-fold lower (&amp;lt;10%) than in serum (5900\u00a0pg mL\n                      <jats:sup>-1<\/jats:sup>\n                      on the 10th day postpartum, 24\u00a0h after the last dose and at the beginning of breast milk collection).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Considering the low oral availability (\u223c15%) of sirolimus and the concentration found in breast milk, sirolimus is expected to achieve serum concentrations in the newborn below minimum therapeutic concentrations. The assessment of drug exposure in neonatal serum was not possible, as breastfeeding was not recommended. Thus, more studies are needed to characterize infant serum sirolimus concentrations and confirm its safety. Nevertheless, this research provides valuable information for breastfeeding counseling and respective guidelines, especially in patients with an increased risk of prematurity, in whom breast milk benefits are even more important.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1859156","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:46:14Z","timestamp":1782452774000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sirolimus excretion in breast milk: a preliminary investigation"],"prefix":"10.3389","volume":"17","author":[{"given":"Estela","family":"Nogueira","sequence":"first","affiliation":[{"name":"Nephrology and Renal Transplantation Department, Unidade Local de Sa\u00fade Santa Maria","place":["Lisbon, Portugal"]},{"name":"Lisbon Academic Medical Center, Faculty of Medicine, Lisbon University","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia","family":"Bento da Silva","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Lisbon University","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Rebelo","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Department, Unidade Local de Sa\u00fade Santa Maria","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ant\u00f3nio","family":"Lopes","sequence":"additional","affiliation":[{"name":"Nephrology and Renal Transplantation Department, Unidade Local de Sa\u00fade Santa Maria","place":["Lisbon, Portugal"]},{"name":"Lisbon Academic Medical Center, Faculty of Medicine, Lisbon University","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria do Ros\u00e1rio","family":"Bronze","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Lisbon University","place":["Lisbon, Portugal"]},{"name":"IBET, Instituto de Biologia Experimental e Tecnol\u00f3gica","place":["Oeiras, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9lia","family":"Duarte","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Lisbon University","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1038\/s41372-024-01868-9","article-title":"Sirolimus for vascular anomalies in the first year of life: a systematic review","volume":"44","author":"Cavazos","year":"2024","journal-title":"J. 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