{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:49:28Z","timestamp":1765547368056,"version":"3.40.4"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Famotidine, a H<jats:sub>2<\/jats:sub>\u2010receptor antagonist, is commonly used to treat heartburn and gastroesophageal reflux disease during pregnancy. However, information on the pharmacokinetics (PK) of famotidine in pregnant patients is limited since pregnant patients are usually excluded from clinical trials. This study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for famotidine in non\u2010pregnant and pregnant populations, and to combine it with a pharmacodynamic (PD) model to predict the effect of famotidine on intragastric pH. Clinical data for model evaluation were taken from the literature. The PBPK model successfully predicted famotidine PK in non\u2010pregnant and pregnant populations. The ratio of predicted versus observed PK parameters in non\u2010pregnant populations ranged from 0.66 to 1.33 for the area under the concentration\u2013time curve and from 0.50 to 1.27 for peak concentration (C<jats:sub>max<\/jats:sub>). In the pregnant populations, these ratios were 0.94 and 1.17 for early pregnancy, 0.82 and 1.29 for mid\u2010pregnancy, and 0.72 and 1.06 for late pregnancy, respectively. Compared to the non\u2010pregnant population, famotidine exposure was predicted to be decreased by, on average, 24% in mid\u2010pregnancy and 20% in late pregnancy. The PBPK\/PD model adequately captured the increase in intragastric pH observed in non\u2010pregnant adults after famotidine intake and suggested a similar effect in mid\u2010 and late pregnancy. High inter\u2010individual variability and minor discrepancies between model predictions and clinical observations indicate a need for further clinical data to reliably inform dosing strategies and therapeutic outcomes for famotidine in pregnant populations.<\/jats:p>","DOI":"10.1002\/jcph.6185","type":"journal-article","created":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T04:35:06Z","timestamp":1736570106000},"page":"564-574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Physiologically based Pharmacokinetic\/Pharmacodynamic Modeling (PBPK\/PD) of Famotidine in Pregnancy"],"prefix":"10.1002","volume":"65","author":[{"given":"Xiaomei I.","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Children's National Hospital  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dionna J.","family":"Green","sequence":"additional","affiliation":[{"name":"Office of Pediatric Therapeutics US Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"van den Anker","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Children's National Hospital  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Homa K.","family":"Ahmadzia","sequence":"additional","affiliation":[{"name":"Division of OBGYN George Washington Medical Center  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin","family":"Calderon","sequence":"additional","affiliation":[{"name":"Division of OBGYN George Washington Medical Center  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2005-9301","authenticated-orcid":false,"given":"Gilbert J.","family":"Burckart","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology US Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1108-5719","authenticated-orcid":false,"given":"Andr\u00e9","family":"Dallmann","sequence":"additional","affiliation":[{"name":"Bayer HealthCare SAS Lille, France, on behalf of: Model\u2010Informed Drug Development, Research and Development Pharmaceuticals, Bayer AG  Leverkusen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.02.029"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3138\/ijfab.1.2.5"},{"key":"e_1_2_9_4_1","unstructured":"US Food and Drug Administration: Guidance for Industry: Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials April 2018. Accessed November 16 2023.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/pregnant\u2010women\u2010scientific\u2010and\u2010ethical\u2010considerations\u2010inclusion\u2010clinical\u2010trials"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199911)60:5<306::AID-TERA11>3.0.CO;2-Y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c22-00685"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12473"},{"key":"e_1_2_9_8_1","unstructured":"The R Project for Statistical Computing. Accessed July 12 2023.https:\/\/www.R\u2010project.org\/"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12134"},{"key":"e_1_2_9_10_1","unstructured":"US Food and Drug Administration: Famotidine June2022. 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