{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:03:41Z","timestamp":1789700621870,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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>The current investigation introduces single\u2010cell physiologically based pharmacokinetic (scPBPK) models to gain insight into drug disposition at the cellular scale. The transition from standard PBPK (sPBPK) models to scPBPK models required depiction of expression\u2010dependent (ED) processes, such as drug metabolism or membrane transport. ED processes utilize weighting functions\u2014a defined or data\u2010driven distribution\u2014that yield heterogeneity in individual cell kinetics. Two scPBPK model examples are provided, one involving a drug (AZD1775) subject to three ED blood\u2013brain barrier transport processes, and another drug (midazolam) with a single ED process of metabolism by hepatocytes. For both examples, the weighting function for each ED process was defined by a negative binomial distribution that is often used in scRNAseq analytics. The AZD1775 model simulations indicated a large degree of single\u2010cell drug concentration heterogeneity, whereas those for midazolam did not due to high membrane transport relative to metabolism. scPBPK models offer a means to probe cellular pharmacokinetics compatible with modern omic technologies and may be extended to pharmacodynamic models.<\/jats:p>","DOI":"10.1002\/psp4.70320","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T03:38:28Z","timestamp":1787283508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Introduction to Single\u2010Cell Physiologically\u2010Based Pharmacokinetic (\n                    <scp>scPBPK<\/scp>\n                    ) Models"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-3900","authenticated-orcid":false,"given":"Anshul","family":"Saini","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences  Buffalo New York USA"},{"name":"Department of Systems Biology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-4817","authenticated-orcid":false,"given":"James M.","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600721003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03274-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-025-01155-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200221999210101233340"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3289"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00580-2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00615-w"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1693388"},{"key":"e_1_2_9_10_1","first-page":"71","volume-title":"Methods in Molecular Biology","author":"Zhu A. 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