{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T03:07:50Z","timestamp":1778728070160,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Elafibranor 80\u2009mg\/day is approved for second\u2010line primary biliary cholangitis (PBC) treatment. We present pharmacokinetic (PK) analyses of elafibranor and its metabolite, GFT1007, and pharmacokinetic\u2010pharmacodynamic (PKPD) analyses describing the relationship between their exposure and responses in alkaline phosphatase (ALP) and total bilirubin (TB). PK data originated from 17 clinical trials. Separate elafibranor and GFT1007 PK models were developed using nonlinear mixed\u2010effects modeling. Effects of covariates on PK parameters were explored. PKPD data originated from one phase II and one phase III trial; separate ALP and TB models were developed using a sequential approach. The sum of the areas under the plasma\u2010concentration time curve during a dosing interval at steady state of elafibranor and GFT1007 (AUC\n                    <jats:sub>\u03c4,ss sum<\/jats:sub>\n                    ) from the PK models was used as a driver for drug effects. A joint ALP\u2010TB model, considering correlations in the inter\u2010individual variability on selected parameters, was developed and used to perform simulations. Elafibranor and GFT1007 are described by structurally similar two\u2010compartmental models. Elafibranor has a longer elimination half\u2010life versus GFT1007 (59.7 versus 10.7\u2009h); predicted time to steady state was 12.4 versus 2.22\u2009days. Covariate effects on the PK of elafibranor and GFT1007 had a limited effect on the PD response of patients receiving the 80\u2009mg\/day regimen. Based on PKPD simulations, elafibranor 80\u2009mg\/day showed a clear effect and improvement in ALP and TB versus placebo. Saturation in ALP responses was observed for &gt;\u200930\u2009\u03bcmol\u00b7h\/L, reached by around 60% of patients. These analyses support that elafibranor 80\u2009mg\/day is an efficacious PBC treatment.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70247","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:24:28Z","timestamp":1776684268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Pharmacokinetics\u2010Pharmacodynamics Analyses of Elafibranor to Support Dose Selection in Primary Biliary Cholangitis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-9842","authenticated-orcid":false,"given":"Qing Xi","family":"Ooi","sequence":"first","affiliation":[{"name":"Pharmetheus  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7551-0758","authenticated-orcid":false,"given":"Karl","family":"Brendel","sequence":"additional","affiliation":[{"name":"Ipsen  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stijn","family":"van Beek","sequence":"additional","affiliation":[{"name":"Pharmetheus  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8680-3792","authenticated-orcid":false,"given":"Jurij Aguiar","family":"Zdovc","sequence":"additional","affiliation":[{"name":"Pharmetheus  Uppsala Sweden"},{"name":"Faculty of Pharmacy University of Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maddlie","family":"Bardol","sequence":"additional","affiliation":[{"name":"Pharmetheus  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Dehez","sequence":"additional","affiliation":[{"name":"Ipsen  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30145"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15329"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80098-1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.08.029"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2021.1945919"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509840"},{"key":"e_1_2_10_9_1","unstructured":"FDA \u201cIQIRVO\u00ae HIGHLIGHTS OF PRESCRIBING INFORMATION \u201d(2024) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/218860s000lbl.pdf."},{"key":"e_1_2_10_10_1","unstructured":"EMA \u201cIQIRVO\u00ae SUMMARY OF PRODUCT CHARACTERISTICS \u201d(2024) https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/iqirvo\u2010epar\u2010product\u2010information_en.pdf."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0093"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.01.013"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.01.038"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2306185"},{"key":"e_1_2_10_15_1","unstructured":"ClinicalTrials.gov \u201cNCT02704403. Phase 3 Study to Evaluate the Efficacy and Safety of Elafibranor Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH) (RESOLVE\u2010IT) \u201d(2024) https:\/\/clinicaltrials.gov\/study\/NCT02704403."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2025.04.025"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12838"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012998.04442.1f"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012999.36063.4e"},{"key":"e_1_2_10_20_1","first-page":"S2209","article-title":"The Efficacy of Elafibranor is not Affected by Body Mass Index in Patients With Primary Biliary Cholangitis","volume":"82","author":"Kremer A.","year":"2025","journal-title":"Hepatology"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70247","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70247","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70247","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T02:17:44Z","timestamp":1778725064000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/psp4.70247"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70247","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"assertion":[{"value":"2025-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70247"}}