{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T22:27:35Z","timestamp":1775082455785,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.18512.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000}}],"reference-count":22,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"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":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Data surrounding the exposure of the breastfed infant to drugs and any associated risks are sparse. Drugs usually are transferred to milk in small quantities, and many have been used without obviously noticeable infant toxicity for many years \u2013 this lack of a \u2018safety signal\u2019 has further reduced the interest in studying mother-to-infant transfer of the drugs. In sub-Saharan Africa, pregnant women are at risk of\u00a0\n                    <ns4:italic>Plasmodium falciparum<\/ns4:italic>\n                    \u00a0infection, and one in four women have evidence of placental infection at the time of delivery. Artemisinin-based combination therapies (ACTs), primarily artemether-lumefantrine (AL), are the current first-line treatment for uncomplicated\n                    <ns4:italic>Plasmodium falciparum<\/ns4:italic>\n                    malaria, with the same dosing recommendations in breastfeeding women as those in the adult population. Dihydroartemisinin-piperaquine (DP) is routinely used as an alternative to AL in Uganda. However, lactation pharmacokinetics (PK) of ACTs are unknown. Pharmacokinetic characterization of anti-malarial transfer to breast milk and breastfed infants is crucial in understanding the potential consequences to the infant, in terms of therapeutic- and prophylactic effects as well as potential toxicity.\u00a0\u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    This observational study will enroll 30 mother-infant pairs, and aims to characterize the breastmilk transfer of antimalarial medications (AL and DP) to infants when these ACTs are administered to mothers as part of treatment for uncomplicated malaria. In addition, we will assess the mental health of the breastfeeding mothers enrolled as well as the well-being of their children.\n                  <\/ns4:p>\n                  <ns4:p>PK samples of maternal blood, breastmilk and breastfeeding infant\u2019s blood will be obtained at specific times points. Pharmacokinetic data will be analyzed using a population pharmacokinetic approach.<\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    We anticipate that findings from this research will guide to develop a PK model describing lumefantrine and piperaquine disposition and will provide a framework to foster other lactation pharmacokinetic studies in different disease areas.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.18512.2","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T13:35:16Z","timestamp":1691674516000},"page":"12","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["\u00adPharmacokinetics of antimalarial drugs used to treat uncomplicated malaria 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":"Turyahabwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon Peter","family":"Asiimwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnson","family":"Magoola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0757-5259","authenticated-orcid":false,"given":"Clifford George","family":"Banda","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":[[2023,8,10]]},"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":"1296-7","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","article-title":"Clinical Lactation Studies: Considerations for Study Design. 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research involving humans as research participants.","year":"2014"},{"key":"ref-17","first-page":"67-73","article-title":"Bioanalytical method development and validation: from the USFDA 2001 to the USFDA 2018 guidance for industry.","volume":"4","author":"R Meesters","year":"2018"},{"key":"ref-18","first-page":"184-5","article-title":"Estimating of the amount of artemether and lumefantrine excreted through breast milk.","volume":"20","author":"J Jain","year":"2015","journal-title":"Tropical Medicine and International Health."},{"key":"ref-19","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-235","article-title":"Population pharmacokinetics of mefloquine, piperaquine and artemether-lumefantrine in Cambodian and Tanzanian malaria patients.","volume":"12","author":"E Staehli Hodel","year":"2013","journal-title":"Malar J."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"e88","DOI":"10.1038\/psp.2013.71","article-title":"Basic concepts in population modeling, simulation, and model-based drug development: part 3-introduction to pharmacodynamic modeling methods.","volume":"3","author":"R Upton","year":"2014","journal-title":"CPT Pharmacometrics Syst Pharmacol."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"1702-6","DOI":"10.1345\/aph.1D374","article-title":"Population pharmacokinetics I: background, concepts, and models.","volume":"38","author":"E Ette","year":"2004","journal-title":"Ann Pharmacother."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"81-93","DOI":"10.2165\/00003088-199630020-00001","article-title":"The use of population pharmacokinetics in drug development.","volume":"30","author":"S Vozeh","year":"1996","journal-title":"Clin Pharmacokinet."}],"container-title":["Wellcome Open 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.22003.r65001, Andre Daher, Oswaldo Cruz Foundation, Rio de Janeiro, 24 Aug 2023, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-12\/v2#referee-response-65001","order":0,"name":"referee-response-65001","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.22003.r65000, Mary Ellen Gilder, Shoklo Malaria Research Unit, Mae Sot, Tak, 19 Sep 2023, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-12\/v2#referee-response-65000","order":1,"name":"referee-response-65000","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [222075, <a href=https:\/\/doi.org\/10.35802\/222075>https:\/\/doi.org\/10.35802\/222075<\/a>] 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":2,"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"}]}}