{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T15:36:23Z","timestamp":1771860983177,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008340","name":"Elsass Fonden","doi-asserted-by":"publisher","award":["18\u20103\u20100451"],"award-info":[{"award-number":["18\u20103\u20100451"]}],"id":[{"id":"10.13039\/501100008340","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aim of the study was to investigate whether differences in paracetamol pharmacokinetics (PK) between spinal muscular atrophy (SMA) patients and healthy controls (HC) could be attributed to specific clinical covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Nonlinear mixed\u2010effects modelling (NONMEM 7.4) was used to develop a population PK model, explore covariates for paracetamol and its metabolites and perform simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>With body weight as allometric scaling in the model, SMA disease resulted in a 58% (95% confidence interval [CI]: 20%\u2013130%) increase in the volume of distribution for paracetamol and its metabolites compared to healthy controls. Decreased plasma myoglobin and plasma bilirubin concentrations, seen in SMA patients, resulted in a higher paracetamol leftover clearance (SMA, median: 13.30\u2009L\/h\/70\u2009kg, 95% CI: 9.14\u201318.29%; HC, median: 4.05\u2009L\/h\/70\u2009kg, 95% CI: 3.38\u20138.83%) and a shift from slower sulfate formation clearance (SMA, median: 8.78\u2009L\/h\/70\u2009kg, 95% CI: 7.22\u20139.61%; HC, median: 9.30\u2009L\/h\/70\u2009kg, 95% CI: 8.42\u201310.15%) and faster oxidative metabolites elimination clearance (SMA, median: 3.74\u2009L\/h\/70\u2009kg, 95% CI: 3.31\u20134.72%; HC, median: 3.25\u2009L\/h\/70\u2009kg, 95% CI: 2.87\u20133.92%). Simulations revealed that in SMA patients, higher bodyweight was associated with increased exposure to paracetamol and its metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The differences in PK between SMA patients and healthy controls could be explained by body weight and the disease itself. SMA patients should be dosed cautiously, ensuring doses do not exceed the recommended body weight adjusted limit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70028","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T06:04:32Z","timestamp":1741759472000},"page":"2045-2056","source":"Crossref","is-referenced-by-count":3,"title":["Paracetamol and its metabolites in children and adults with spinal muscular atrophy \u2013 a population pharmacokinetic model"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5800-0966","authenticated-orcid":false,"given":"Qiaolin","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus University Medical Center Rotterdam  Rotterdam the Netherlands"},{"name":"Rotterdam Clinical Pharmacometrics Group  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie Mostue","family":"Naume","sequence":"additional","affiliation":[{"name":"Copenhagen Neuromuscular Center, Department of Neurology Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Science University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-8443","authenticated-orcid":false,"given":"Brenda C. 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