{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:12:27Z","timestamp":1772169147199,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.19113.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000}},{"DOI":"10.12688\/wellcomeopenres.19113.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000}},{"DOI":"10.12688\/wellcomeopenres.19113.3","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000}}],"reference-count":19,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust Clinical Research Career Development Fellowship","award":["222075"],"award-info":[{"award-number":["222075"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>Background Globally, more than half of women take medicines whilst breastfeeding. Data concerning the exposure of the breastfed infant to drugs and any related risks are sparce. Lactation studies are only rarely performed close to licensing for medicines anticipated to be widely used in women of childbearing age. Medicines taken by breastfeeding mothers on tuberculosis (TB) treatment can be transferred to the breastfed infant. Potential effects of anti-tuberculosis medicines on nursing infants are not well understood. Similarly, women face mental health challenges while taking medications, including postpartum depression, hence the need to assess the psychological behavior of a breastfeeding woman. Potential risks are the development of adverse drug effects in the breastfed infant and selection for resistance, whereas potential benefits might include exposure to potentially prophylactic concentrations of the drug. Pharmacokinetic studies are therefore necessary to understand this situation fully. Methods This study will enroll 20 mothers receiving first-line anti-tuberculosis medicines, together with their breastfed infants, with the aim of characterizing the breastmilk transfer of the medicines from the mother to the infants. Samples of maternal blood, breastmilk, and breastfeeding infant\u2019s blood will be obtained at specific time points for bioanalysis of drug concentrations. Pharmacokinetic data will be analyzed using a population pharmacokinetic approach. Additionally, the study will assess the psychological status of breastfeeding women and the well-being of their infants. Maternal depression is linked to long-term negative consequences for the infant\u2019s physiological regulation, poor growth-promoting setting for the infants, and inappropriate interactive conduct, characterized by low compassion, constrained range of emotional expression, and varying provision of the infant\u2019s budding engagement. Conclusions This study will provide the first systematic characterization of mother-to-infant transfer of first-line anti-tuberculosis medicines through breast milk. A mathematical pharmacokinetics model characterizing plasma-to-breastmilk transfer of rifampicin, isoniazid, ethambutol, and pyrazinamide will be developed and used to characterize infant exposure through breast milk. Our findings will contribute towards treatment optimization in breastfeeding and provide a framework to foster other lactation pharmacokinetic studies.<\/ns3:p>","DOI":"10.12688\/wellcomeopenres.19113.4","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T12:55:27Z","timestamp":1723467327000},"page":"216","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of drugs used to treat drug sensitive-tuberculosis in breastfeeding mother-infant pairs: An observational pharmacokinetic study"],"prefix":"10.12688","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6626-0329","authenticated-orcid":false,"given":"Ritah","family":"Nakijoba","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7975-0178","authenticated-orcid":false,"given":"Aida","family":"Nakayiwa Kawuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis Williams","family":"Ojara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jovia C.","family":"Tabwenda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Kyeyune","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Turyamureba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9804-6079","authenticated-orcid":false,"given":"Simon","family":"Peter Asiimwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnson","family":"Magoola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Castelnuovo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Buzibye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0134-5855","authenticated-orcid":false,"given":"Catriona","family":"Waitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","DOI":"10.1186\/s13006-015-0053-6","article-title":"Postpartum women's use of medicines and breastfeeding practices: a systematic review.","volume":"10","author":"M Saha","year":"2015","journal-title":"Int Breastfeed J."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"1296-1297","DOI":"10.1056\/NEJMp1817420","article-title":"\"Is it safe?\" - The many unanswered questions about medications and breast-feeding.","volume":"380","author":"J Byrne","year":"2019","journal-title":"N Engl J Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fphar.2019.00005","article-title":"Exposure of infants to isoniazid via breast milk after maternal drug intake of recommended doses is clinically insignificant irrespective of metaboliser status. 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Solans, University of California, Los Angeles, 03 Jul 2024, version 3, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-216\/v3#referee-response-84001","order":1,"name":"referee-response-84001","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.23911.r85075, Eric Decloedt, Stellenbosch University, Stellenbosch, 18 Jun 2024, version 3, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-216\/v3#referee-response-85075","order":2,"name":"referee-response-85075","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [222075], a Wellcome Trust Clinical Research Career Development Fellowship awarded to Catriona Waitt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}