{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:05:06Z","timestamp":1784203506497,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Paracetamol may improve renal function in patients with severe\n                    <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                    malaria, particularly in those with acute kidney injury and hemolysis, via inhibition of cell\u2010free hemoglobin mediated oxidative kidney damage. We developed a population pharmacokinetic\/pharmacodynamic (PK\/PD) model to assess effects of paracetamol on creatinine, hepatotoxicity, fever clearance, and parasite clearance among Malaysian patients with predominantly non\u2010severe knowlesi malaria using data from the PACKNOW trial (Clinical Trials Registration: NCT03056391). A total of 372 patients were included in the PK\/PD analyses (paracetamol:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009183, control:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009189). Paracetamol PK was described using a prior PK model published in patients with falciparum malaria. The PK\/PD demonstrated that higher paracetamol exposures were associated with a faster decline in both creatinine and fever clearance time, supporting its renoprotective and antipyretic effects. Increased paracetamol exposure was not associated with hepatotoxicity or serious adverse events, despite a weak positive association with liver transaminases over time. No significant relationship was observed between paracetamol exposure and parasite clearance. Overall, these findings highlight an exposure\u2010response relationship for paracetamol and a decline in creatinine, supporting its use as a renoprotective drug in treating\n                    <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                    malaria.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70283","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:42:29Z","timestamp":1782128549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Pharmacodynamics of Paracetamol in Malaysian Patients With\n                    <i>Plasmodium knowlesi<\/i>\n                    Malaria"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-4665","authenticated-orcid":false,"given":"Thanaporn","family":"Wattanakul","sequence":"first","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 Oxford University  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3643-7605","authenticated-orcid":false,"given":"Daniel J.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research and Charles Darwin University  Darwin Northern Territory Australia"},{"name":"Infectious Diseases Society Sabah\u2010Menzies School of Health Research Clinical Research Unit  Kota Kinabalu Sabah Malaysia"},{"name":"Department of Medicine University of Cambridge School of Clinical Medicine  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3596-3267","authenticated-orcid":false,"given":"Katherine","family":"Plewes","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 Oxford University  Oxford UK"},{"name":"University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9914-8352","authenticated-orcid":false,"given":"Matthew J.","family":"Grigg","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research and Charles Darwin University  Darwin Northern Territory Australia"},{"name":"Infectious Diseases Society Sabah\u2010Menzies School of Health Research Clinical Research Unit  Kota Kinabalu Sabah Malaysia"},{"name":"Institute for Health Research University of Notre Dame Australia  Fremantle Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-476X","authenticated-orcid":false,"given":"Giri S.","family":"Rajahram","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research and Charles Darwin University  Darwin Northern Territory Australia"},{"name":"Infectious Diseases Society Sabah\u2010Menzies School of Health Research Clinical Research Unit  Kota Kinabalu Sabah Malaysia"},{"name":"Department of Medicine Queen Elizabeth Hospital II, Ministry of Health Malaysia  Kota Kinabalu Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2195-6736","authenticated-orcid":false,"given":"Timothy","family":"William","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research and Charles Darwin University  Darwin Northern Territory Australia"},{"name":"Infectious Diseases Society Sabah\u2010Menzies School of Health Research Clinical 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-1514","authenticated-orcid":false,"given":"Geoffrey W.","family":"Birrell","sequence":"additional","affiliation":[{"name":"Department of Drug Evaluation Australian Defence Force Malaria and Infectious Disease Institute  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2192-0506","authenticated-orcid":false,"given":"Nicholas M.","family":"Anstey","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research and Charles Darwin University  Darwin Northern Territory Australia"},{"name":"Infectious Diseases Society Sabah\u2010Menzies School of Health Research Clinical Research Unit  Kota Kinabalu Sabah Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-912X","authenticated-orcid":false,"given":"Richard 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