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Similar changes in patients with autosomal dominant polycystic kidney disease (ADPKD) may predispose them to drug\u2010induced liver injury (DILI) and hepatic drug\u2013drug interactions (DDIs). Systemic coproporphyrin\u2010I (CP\u2010I), an endogenous biomarker for hepatic OATP1B function and MRP2 substrate, is used to evaluate OATP1B\u2010mediated DDI risk in humans. In this clinical observational cohort\u2010comparison study, bile acid profiles and CP\u2010I concentrations in healthy volunteers and patients with ADPKD were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum and urine samples from healthy volunteers (<jats:italic>n<\/jats:italic>\u2009=\u200916) and patients with ADPKD (<jats:italic>n<\/jats:italic>\u2009=\u20098) were collected. Serum bile acids, and serum and urine CP\u2010I concentrations, were quantified by ultra\u2010performance liquid chromatography tandem mass spectrometry (UPLC\u2010MS\/MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with ADPKD exhibited increased serum concentrations of total (1.3\u2010fold) and taurine\u2010conjugated (2.8\u2010fold) bile acids compared to healthy volunteers. Specifically, serum concentrations of six bile acids known to be more hydrophobic\/hepatotoxic (glycochenodeoxycholate, taurochenodeoxycholate, taurodeoxycholate, lithocholate, glycolithocholate and taurolithocholate) were increased (1.5\u2010, 2.9\u2010, 2.8\u2010, 1.6\u2010, 1.7\u2010 and 2.7\u2010fold, respectively) in patients with ADPKD. Furthermore, serum CP\u2010I concentrations were elevated and the renal clearance of CP\u2010I was reduced in patients with ADPKD compared to healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Increased exposure to bile acids may increase susceptibility to DILI in some patients with ADPKD. Furthermore, the observed increase in serum CP\u2010I concentrations could be attributed, in part, to impaired OATP1B function in patients with ADPKD, which could increase the risk of DDIs involving OATP1B substrates compared to healthy volunteers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16221","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T12:30:58Z","timestamp":1727267458000},"page":"353-364","source":"Crossref","is-referenced-by-count":4,"title":["Altered bile acid and coproporphyrin\u2010I disposition in patients with autosomal dominant polycystic kidney disease"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9977-1184","authenticated-orcid":false,"given":"Jacqueline B.","family":"Tiley","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6926-8844","authenticated-orcid":false,"given":"James J.","family":"Beaudoin","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7662-7497","authenticated-orcid":false,"given":"Vimal K.","family":"Derebail","sequence":"additional","affiliation":[{"name":"UNC Kidney Center, Division of Nephrology and Hypertension, UNC School of Medicine University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7476-9248","authenticated-orcid":false,"given":"William A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-9959","authenticated-orcid":false,"given":"Christine C.","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2565-7004","authenticated-orcid":false,"given":"Justin A.","family":"Veeder","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9696-3164","authenticated-orcid":false,"given":"Lana","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-2136","authenticated-orcid":false,"given":"Jessica L.","family":"Beers","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3739-8994","authenticated-orcid":false,"given":"Wei","family":"Jia","sequence":"additional","affiliation":[{"name":"University of Hawaii Cancer Center  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-6031","authenticated-orcid":false,"given":"Paul W.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, UNC Gillings School of Global Public Health University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-4929","authenticated-orcid":false,"given":"Kim L. 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