{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:08:08Z","timestamp":1778659688043,"version":"3.51.4"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T00:00:00Z","timestamp":1520553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res & Perspec"],"published-print":{"date-parts":[[2018,4]]},"abstract":"Abstract<\/jats:title>This study was conducted to evaluate the likelihood of daprodustat to act as a perpetrator in drug\u2013drug interactions (DDI<\/jats:styled-content>) with the CYP<\/jats:styled-content>2C8 enzyme and OATP<\/jats:styled-content>1B1 transporter using the probe substrates pioglitazone and rosuvastatin as potential victims, respectively. Additionally, this study assessed the effect of a weak CYP<\/jats:styled-content>2C8 inhibitor, trimethoprim, as a perpetrator of a DDI<\/jats:styled-content> with daprodustat.<\/jats:p>This was a two\u2010part study: Part A assessed the effect of coadministration of daprodustat on the pharmacokinetics of pioglitazone and rosuvastatin in 20 subjects; Part B assessed the coadministration of trimethoprim on the pharmacokinetics of daprodustat in 20 subjects.<\/jats:p>Coadministration of 100\u00a0mg of daprodustat with pioglitazone or rosuvastatin had no effect on the plasma exposures of either probe substrate. When trimethoprim was coadministered with 25\u2010mg daprodustat plasma daprodustat AUC<\/jats:styled-content> and C<\/jats:italic>max<\/jats:sub> increased by 48% and 28%, respectively. Additionally, AUC<\/jats:styled-content> and C<\/jats:italic>max<\/jats:sub> for the metabolite GSK<\/jats:styled-content>2531401 were decreased by 32% and 40%, respectively. C<\/jats:italic>max<\/jats:sub> for the other metabolites was slightly decreased (~8\u201315%) but no changes in AUC<\/jats:styled-content> were observed.<\/jats:p>As 100\u2010mg daprodustat exceeds the planned top therapeutic dose, interaction potential of daprodustat as a perpetrator with substrates of the CYP<\/jats:styled-content>2C8 enzyme and OATP<\/jats:styled-content>1B1 transporters is very low. Conversely, daprodustat exposure (AUC<\/jats:styled-content> and C<\/jats:italic>max<\/jats:sub>) is likely to increase moderately with coadministration of weak CYP<\/jats:styled-content>2C8 inhibitors.<\/jats:p>","DOI":"10.1002\/prp2.327","type":"journal-article","created":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T05:56:35Z","timestamp":1520574995000},"source":"Crossref","is-referenced-by-count":17,"title":["The drug interaction potential of daprodustat when coadministered with pioglitazone, rosuvastatin, or trimethoprim in healthy subjects"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7176-1526","authenticated-orcid":false,"given":"Stephen","family":"Caltabiano","sequence":"first","affiliation":[{"name":"Metabolic Pathways GlaxoSmithKline Collegeville Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly M.","family":"Mahar","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling & Simulation GlaxoSmithKline Upper Merion Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karyn","family":"Lister","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Science & Study Operations GlaxoSmithKline Collegeville Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Tenero","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling & Simulation GlaxoSmithKline Upper Merion Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramiya","family":"Ravindranath","sequence":"additional","affiliation":[{"name":"Clinical Statistics GlaxoSmithKline Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borut","family":"Cizman","sequence":"additional","affiliation":[{"name":"Metabolic Pathways GlaxoSmithKline Collegeville Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander R.","family":"Cobitz","sequence":"additional","affiliation":[{"name":"Metabolic Pathways GlaxoSmithKline Collegeville Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,9]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"SA\u2010OR114","article-title":"Daprodustat, a HIF\u2010prolyl\u2010hydroxylase inhibitor, maintains hemoglobin levels over 24\u00a0weeks in anemic hemodialysis subjects switching from recombinant human erythropoietin","volume":"27","author":"Cobitz AR","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-005-0042-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-8525"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2012.12.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014111139"},{"key":"e_1_2_9_7_1","first-page":"TH\u2010PO908","article-title":"Daprodustat, a HIF\u2010prolyl\u2010hydroxylase inhibitor, increases and maintains hemoglobin over 24\u00a0weeks in anemic chronic kidney disease subjects","volume":"27","author":"Holdstock L","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02263.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.83"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(03)80336-3"},{"key":"e_1_2_9_11_1","unstructured":"RizwanA ConnellyK JangI\u2010J ShinJ\u2010G MorrillJ OuelletD et\u00a0al. (2010). Validation of a Seven\u2010Probe Cytochrome P450\/Transporter Cocktail Using Known Inhibitors. American Association of Pharmaceutical Scientists \u20102010 Annual Meeting & Exposition 2010; PSWC2010\u2010002394."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2016.1182981"},{"key":"e_1_2_9_13_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)(2016). Guidance for Industry: Drug Interaction Studies \u2013 Draft Guidance \u2013 Study design data Analysis Implications for Dosing and Labelling recommendations. 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