{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:07:29Z","timestamp":1784549249413,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Two Phase 1 open\u2010label studies were conducted in otherwise healthy participants, with BMI classified as overweight\/obesity, to assess the potential of lotiglipron (a glucagon\u2010like peptide\u20101 receptor agonist) as precipitant for pharmacokinetic (PK) drug\u2013drug interactions (DDIs) when co\u2010administered with substrates of cytochrome P450 (CYP) 3A (midazolam and oral contraceptive containing levonorgestrel\/ethinyl estradiol [LE\/EE]) and CYP2C19 (omeprazole) enzymes, and substrates of p\u2010glycoprotein (dabigatran), breast cancer resistance protein and organic anion transporting polypeptide transporters (rosuvastatin). Potential PK DDI between semaglutide and midazolam was also assessed. Co\u2010administration with lotiglipron led to modest dose\u2010dependent decreases in midazolam area under the concentration\u2013time curve (AUC) (up to 30%), no clinically relevant changes in exposures of oral contraceptive (LE\/EE), substantial reductions in omeprazole AUC (up to 70%) and clinically relevant increases in rosuvastatin AUC (up to 2.3\u2010fold). Upon co\u2010administration with lotiglipron, maximum observed plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ) of dabigatran decreased (up to 55%) with no significant changes in AUC. No significant changes were observed in midazolam exposure (AUC\n                    <jats:sub>inf<\/jats:sub>\n                    and C\n                    <jats:sub>max<\/jats:sub>\n                    ) following co\u2010administration with semaglutide. Across both studies a subset of lotiglipron\u2010treated participants (31% and 19% in Studies 1 and 2, respectively) had elevations in liver transaminases (alanine\/aspartate aminotransferase &gt;3 \u00d7 ULN), which (based on PK data) were associated with reduced ability of the liver to transport\/metabolize drugs cleared by multiple pathways. Based on the results of the two Phase 1 studies reported here along with the results of a Phase 2 study where transaminases elevations were also noted, both Phase 1 studies were prematurely terminated along with the clinical development of lotiglipron.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>ClinicalTrials.gov identifiers<\/jats:bold>\n                    : NCT05671653; NCT05788328.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70158","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T14:06:38Z","timestamp":1777471598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of the Drug\u2013Drug Interaction Potential of Lotiglipron (PF\u201007081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol"],"prefix":"10.1002","volume":"66","author":[{"given":"Carol","family":"Cronenberger","sequence":"first","affiliation":[{"name":"Pfizer Inc.  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