{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:59:35Z","timestamp":1792202375724,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      This study intends to assess the pharmacokinetic properties and treatment response of lumefantrine in pregnant and non\u2010pregnant women with uncomplicated\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      malaria infection in Western Kenya.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seventy\u2010five women with uncomplicated\n                      <jats:italic>P<\/jats:italic>\n                      .\n                      <jats:italic>falciparum<\/jats:italic>\n                      malaria were enrolled, including 25 non\u2010pregnant, 30 pregnant women in the second trimester and 20 pregnant women in their third trimester. The participants received a standard dose of artemether\u2013lumefantrine (80\/480\u2009mg) twice daily for 3\u2009days. Densely venous plasma samples were collected. Nonlinear mixed\u2010effects modelling was used to characterize the pharmacokinetic properties of lumefantrine, and the effects of pregnancy was assessed on all pharmacokinetic parameters by a full covariate modelling approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The concentration\u2010time data of lumefantrine were described adequately by a two\u2010compartment disposition model, with a flexible transit absorption and first\u2010order elimination. Covariate modelling results demonstrated that pregnancy status or gestational age had a significant impact on both elimination clearance (CL) and the central volume of distribution (Vc) of lumefantrine. The estimated pregnancy effects on CL and Vc were 23% (95%CI: 10.8\u201334.8%) and 28% (95%CI: 7.3\u201351.8%), respectively. Pregnant women exhibited lower drug exposure compared to non\u2010pregnant women, with the geometric mean ratios (GMRs) of 0.76 (95% CI: 0.57\u20131.01), 0.79 (95% CI: 0.63\u20130.99) and 0.69 (95% CI: 0.51\u20130.94) for area under the concentration\u2010time curve (AUC), maxinum concentration (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) and Day 7 concentration, respectively. Other covariates did not significantly affect the pharmacokinetics of lumefantrine. The 28\u2010day polymerase chain reaction (PCR)\u2010corrected parasitological cure was 100% for both pregnant and non\u2010pregnant women.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The exposure to lumefantrine was lower in pregnant women, compared to non\u2010pregnant women, with uncomplicated\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      infection. This lower drug exposure might increase the risk of treatment failure with artemether\u2013lumefantrine in pregnant women, especially if susceptibility to either drug is reduced. Continuous assessment and monitoring of the efficacy of artemether\u2013lumefantrine in pregnant women are warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.70318","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:21:53Z","timestamp":1761708113000},"page":"911-921","source":"Crossref","is-referenced-by-count":2,"title":["Population pharmacokinetics of lumefantrine in pregnant and non\u2010pregnant women with uncomplicated\n                    <i>Plasmodium falciparum<\/i>\n                    malaria in Western Kenya"],"prefix":"10.1111","volume":"92","author":[{"given":"Elizabeth","family":"Juma","sequence":"first","affiliation":[{"name":"Centre for Clinical Research Kenya Medical Research Institute  Kisumu Kenya"},{"name":"CREATES Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-3178","authenticated-orcid":false,"given":"Junjie","family":"Ding","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University  Bangkok Thailand"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6838-8417","authenticated-orcid":false,"given":"Martin","family":"Ongas","sequence":"additional","affiliation":[{"name":"CREATES Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Koskei","sequence":"additional","affiliation":[{"name":"CREATES Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Onyango","sequence":"additional","affiliation":[{"name":"CREATES Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Oloo","sequence":"additional","affiliation":[{"name":"CREATES Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Aman","sequence":"additional","affiliation":[{"name":"African Centre for Clinical Trials  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Kokwaro","sequence":"additional","affiliation":[{"name":"Strathmore Business School Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-4030","authenticated-orcid":false,"given":"Joel","family":"Tarning","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University  Bangkok Thailand"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford  Oxford UK"},{"name":"Infectious Diseases Data Observatory, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0992-5654","authenticated-orcid":false,"given":"Bernhards","family":"Ogutu","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research Kenya Medical Research Institute  Kisumu Kenya"},{"name":"CREATES Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"World Health Organization.World malaria report.2024;2004."},{"key":"e_1_2_10_3_1","article-title":"Guidelines for the treatment of malaria third edition","author":"World Health Organization WH","year":"2015","journal-title":"In"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010199937020\u201000002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1508606"},{"key":"e_1_2_10_6_1","volume-title":"National Guidelines for Diagnosis and Treatment and Prevention of Malaria for Health Workers","author":"Mo H","year":"2016"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102125.2002.01696.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.59"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002579"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02595\u201014"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00683\u201013"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01605\u201015"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2021.122887"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010016\u20109487\u20108"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.70015"},{"issue":"2","key":"e_1_2_10_17_1","first-page":"S23","article-title":"The concise guide to PHARMACOLOGY 2023\/24: G protein\u2010coupled receptors","volume":"180","author":"Alexander SPH","year":"2023","journal-title":"Br J Pharmacol"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00267\u201015"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00195\u201009"},{"issue":"1","key":"e_1_2_10_20_1","first-page":"S34","article-title":"Physiologic changes during pregnancy and impact on small\u2010molecule drugs, biologic (monoclonal antibody) disposition, and response","volume":"63","author":"Eke AC","year":"2023","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.08.030"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.043851"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928\u20100987(99)00037\u20108"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2021.100107"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475\u20102875\u20108\u2010S1\u2010S4"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101746"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010024\u201001008\u20102"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201033873\u2010x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2024.09.005"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.70318","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.70318","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.70318","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:29:04Z","timestamp":1773005344000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.70318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/bcp.70318"],"URL":"https:\/\/doi.org\/10.1111\/bcp.70318","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]}}}