{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:05:21Z","timestamp":1789700721816,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Reliable physiologically based pharmacokinetic (PBPK) modeling depends on tissue\u2010specific expression profiles that reflect protein activities governing drug disposition. In PK\u2010Sim, existing expression databases rely on transcriptomics data. However, mRNA levels often exhibit limited correlation with protein abundance, frequently necessitating empirical expression modification to align bottom\u2010up simulations with clinical observations. To address this limitation, we developed ProteinDB as a proteomics\u2010based expression database for PK\u2010Sim, using proteomics data primarily from PaxDb v6.0. Raw proteomics data were mapped to gene identifiers and standardized into absolute concentrations (\u03bcmol\/L tissue) before integration into PK\u2010Sim. Cross\u2010platform comparisons were performed for hepatic protein abundance across PBPK platforms, while cross\u2010omics comparisons were made of relative tissue distributions with transcriptomics\u2010based PK\u2010Sim databases. The performance of ProteinDB in PBPK modeling was evaluated using the probe substrates midazolam, digoxin, rifampicin, and tizanidine, with associated drug\u2013drug interactions. Cross\u2010platform comparisons showed strong agreement for most hepatic enzymes and transporters, while revealing divergences for proteins with greater inter\u2010individual variability, lower abundance, or limited evidence base. Cross\u2010omics analyses demonstrated tissue\u2010dependent discrepancies between transcript\u2010 and protein\u2010based expression patterns, with higher consistency observed for kidney and small intestine, particularly with the RT\u2010PCR and Bgee databases. For PBPK modeling, ProteinDB showed consistently comparable or superior predictive performance for systemic exposure and other clinical endpoints compared with transcriptomics\u2010based baseline and empirically modified library profiles. By providing a direct physiological basis for system parameterization, ProteinDB offers a robust alternative to current transcriptomics PK\u2010Sim databases and reduces the reliance on empirical expression modification, thus improving the reliability of prospective PBPK modeling.<\/jats:p>","DOI":"10.1002\/psp4.70316","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T03:38:12Z","timestamp":1787197092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transitioning from Transcriptomics to Proteomics: Enhancing Mechanistic Accuracy in\n                    <scp>PBPK<\/scp>\n                    Modeling via Absolute Protein Abundances"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5697-999X","authenticated-orcid":false,"given":"Chen","family":"Ning","sequence":"first","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2143-6706","authenticated-orcid":false,"given":"Alessandra","family":"Pugliano","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2995-5061","authenticated-orcid":false,"given":"Maximilian","family":"Winter","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1305-2467","authenticated-orcid":false,"given":"Keliang","family":"Wu","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"},{"name":"School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-7351","authenticated-orcid":false,"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"},{"name":"BioNotus CommV  Niel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.21608\/svu.2019.14193.1020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2016.04.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40495-020-00212-x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40495-016-0059-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12134"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.41"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.043174"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12101001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2012.06.013"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12904"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.132"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2018.02.011"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5716409"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.14"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1103"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45778-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.121.000449"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf1066"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.7b00025"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1071"},{"issue":"5","key":"e_1_2_9_23_1","first-page":"465","article-title":"Integrated Cytochrome P450 Reaction Phenotyping: Attempting to Bridge the Gap Between cDNA\u2010Expressed Cytochromes P450 and Native Human Liver Microsomes","volume":"57","author":"Rodrigues A. 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