{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:24:27Z","timestamp":1790835867479,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005024","name":"Beijing Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Patients with metabolic dysfunction\u2010associated steatotic liver disease (MASLD) may exhibit altered pharmacokinetics (PK) and pharmacodynamics (PD) of drugs compared with healthy populations. However, no physiologically based pharmacokinetic\/pharmacodynamic (PBPK\/PD) model has been specifically developed for MASLD. Acetaminophen (APAP), a widely used analgesic, was selected to develop a PBPK\/PD model predicting PK\/PD changes of APAP and its metabolites in MASLD\u2010related populations. Based on a comprehensive review of published APAP PK studies and examination of existing PBPK models, a simultaneous parent\u2010metabolite PBPK model for APAP was developed and optimized in healthy people. The model simulated the dynamics of APAP and its five major metabolites: APAP\u2010glucuronide (APAP\u2010glu), APAP\u2010sulfate (APAP\u2010sul), N\u2010acetyl\u2010p\u2010benzoquinone imine (NAPQI), APAP\u2010cysteine (APAP\u2010cys), and APAP\u2010mercapturate (APAP\u2010merc). The validated model was expanded to MASLD\u2010related populations, including overweight, obese, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and cirrhosis with different severities. Finally, a PD model was integrated to correlate APAP's PK with pain relief scores. The PBPK model reproduced published clinical PK data for APAP and its metabolites in healthy and MASLD\u2010related populations. At therapeutic doses, the toxic NAPQI remained at very low levels. APAP's pain relief efficacy was retained, but onset time may change in MASLD\u2010related populations. This PBPK\/PD approach provides a strategy for projecting drug exposure in MASLD\u2010related populations, even without specific PK or PD data. It highlights modeling's utility for personalized medicine in MASLD patients and MASLD treatment drug development.<\/jats:p>","DOI":"10.1002\/psp4.70161","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:57:46Z","timestamp":1764136666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the\n                    <scp>PK<\/scp>\n                    \/\n                    <scp>PD<\/scp>\n                    Changes on\n                    <scp>MASLD<\/scp>\n                    \u2010Related Population\u2014An Example From Simultaneous Acetaminophen Parent\u2010Metabolite\n                    <scp>PBPK<\/scp>\n                    \/\n                    <scp>PD<\/scp>\n                    Modeling"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-5710","authenticated-orcid":false,"given":"Shanshan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pharmacy Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-3171","authenticated-orcid":false,"given":"Lan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Xuanwu Hospital Capital Medical University  Beijing 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