{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:12:29Z","timestamp":1773810749071,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"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;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Population pharmacokinetic\u2013pharmacodynamic (PK\u2013PD) modeling was used to explore covariate effects on zolpidem PKs and PDs in 30 healthy Korean volunteers (15 males, 15 females) who received a single 10\u2009mg dose. The dataset included 325 PK observations and 388 observations each for the digit symbol substitution test (DSST), choice reaction time (CRT), and visual analog scale (VAS). A one\u2010compartment PK model with transit compartment absorption and first\u2010order elimination was developed, followed by sequential sigmoid E\n                    <jats:sub>max<\/jats:sub>\n                    \u2010based direct response models for each PD endpoint. A hyperbolic learning effect model was incorporated for DSST, whereas CRT showed no clear learning effect. Baseline VAS was described using linear splines. No clinically meaningful covariates were retained in the final PK or PK\u2013VAS models. In contrast, higher body weight was associated with reduced DSST IC\n                    <jats:sub>50<\/jats:sub>\n                    and CRT EC\n                    <jats:sub>50<\/jats:sub>\n                    . Lower albumin was associated with increased potency for both DSST and CRT and with a steeper concentration\u2010response relationship for CRT. Higher baseline CRT values were linked to greater potency and a steeper slope for CRT, and older age was associated with lower baseline DSST and CRT performance. These exploratory findings suggest that variability in zolpidem response may be partially mediated by physiologically and functionally relevant factors, such as body weight, albumin, age, and baseline PD measures, which could complement sex in individualized risk assessment.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70208","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:29:09Z","timestamp":1772990949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic\u2013Pharmacodynamic Analysis of Zolpidem in Healthy Volunteers: Covariate Contributions to Variability in CNS Responses"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8819-4780","authenticated-orcid":false,"given":"Hyun Chul","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"},{"name":"Kidney Research Institute Seoul National University Medical Research Center  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8801-0323","authenticated-orcid":false,"given":"Jung","family":"Sunwoo","sequence":"additional","affiliation":[{"name":"Clinical Trials Center Chungnam National University Hospital  Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-0045","authenticated-orcid":false,"given":"Seonghae","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Bundang Hospital  Gyeonggi\u2010do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8384-3139","authenticated-orcid":false,"given":"In\u2010Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4188-2786","authenticated-orcid":false,"given":"Jae\u2010Yong","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Bundang Hospital  Gyeonggi\u2010do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pnp.502"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.2021.19.2.367"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105534"},{"key":"e_1_2_9_5_1","unstructured":"Sanofi\u2010Aventis U.S. LLC \u201cAMBIEN (Zolpidem Tartrate) Tablets [Prescribing Information]. U.S. Food and Drug Administration \u201dUpdated February 2022 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/019908s40s044s047lbl.pdf."},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010199529030\u201000002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102125.1999.00953.x"},{"key":"e_1_2_9_8_1","unstructured":"U.S. Food and Drug Administration \u201cQuestions and Answers: Risk of Next\u2010Morning Impairment After Use of Insomnia Drugs; FDA Requires Lower Recommended Doses for Certain Drugs Containing Zolpidem (Ambien Ambien CR Edluar and Zolpimist) \u201dUpdated February 13 2018 https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/questions\u2010and\u2010answers\u2010risk\u2010next\u2010morning\u2010impairment\u2010after\u2010use\u2010insomnia\u2010drugs\u2010fda\u2010requires\u2010lower."},{"key":"e_1_2_9_9_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Drug Safety Communication: Risk of Next\u2010Morning Impairment After Use of Insomnia Drugs; FDA Requires Lower Recommended Doses for Certain Drugs Containing Zolpidem (Ambien Ambien CR Edluar and Zolpimist) \u201dUpdated January 10 2013 https:\/\/wayback.archive\u2010it.org\/7993\/20170404172106\/https:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm334033.htm."},{"key":"e_1_2_9_10_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Drug Safety Communication: FDA Approves New Label Changes and Dosing for Zolpidem Products and a Recommendation to Avoid Driving the Day After Using Ambien CR \u201dUpdated May 14 2013 https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/fda\u2010drug\u2010safety\u2010communication\u2010fda\u2010approves\u2010new\u2010label\u2010changes\u2010and\u2010dosing\u2010zolpidem\u2010products\u2010and."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000001026"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201098689\u2010z"},{"key":"e_1_2_9_13_1","unstructured":"U.S. Food and Drug Administration \u201cPopulation Pharmacokinetics: Guidance for Industry \u201d(2022) https:\/\/www.fda.gov\/media\/128793\/download."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010007\u20109066\u20100"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.71"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ergon.2011.05.001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apm.2017.01.025"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpe.2015.06.021"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13116"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13056"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010016\u20109487\u20108"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010017\u20109542\u20100"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12611"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010011\u20100648\u20106"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13161"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000941"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/17470218.2017.1322622"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1017\/s1355617700611098"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010018\u20100068\u20102"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010018\u20100632\u2010y"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826\u2010200001000\u201000011"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.09r00849bro"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2009.03.004"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.03.022"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.52965\/001c.24927"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010014\u20103447\u2010z"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2004.02.001"}],"container-title":["CPT: Pharmacometrics &amp; 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