{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:59:38Z","timestamp":1790510378189,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T00:00:00Z","timestamp":1534032000000},"content-version":"am","delay-in-days":345,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration (FDA) through Medical Countermeasures initiative","doi-asserted-by":"publisher","award":["U01FD004979"],"award-info":[{"award-number":["U01FD004979"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jpharmsci.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2017,9]]},"DOI":"10.1016\/j.xphs.2017.04.076","type":"journal-article","created":{"date-parts":[[2017,5,6]],"date-time":"2017-05-06T02:30:51Z","timestamp":1494037851000},"page":"2551-2557","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Effect of Uremic Solutes on the Organic Cation Transporter 2"],"prefix":"10.1016","volume":"106","author":[{"given":"Kit Wun Kathy","family":"Cheung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hsiang","family":"Hsueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiew-Mei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Giacomini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.xphs.2017.04.076_bib1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrd3028","article-title":"Membrane transporters in drug development","volume":"9","author":"Giacomini","year":"2010","journal-title":"Nat Rev Drug Discov"},{"issue":"3","key":"10.1016\/j.xphs.2017.04.076_bib2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrd3124","article-title":"Transporters in drug development: advancing on the Critical Path","volume":"9","author":"Huang","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.xphs.2017.04.076_bib3","series-title":"Guidance for Industry. Drug Interaction Studies\u2013Study Design, Data Analysis, and Implications for Dosing and Labeling. Draft Guidance","year":"2012"},{"key":"10.1016\/j.xphs.2017.04.076_bib4","series-title":"Guideline on the Investigation of Drug Interactions. Committee for Human Medicinal Products. European Medicines Agency","year":"2012"},{"key":"10.1016\/j.xphs.2017.04.076_bib5","series-title":"Draft Guideline on Drug Interactions (2013)","year":"2013"},{"key":"10.1016\/j.xphs.2017.04.076_bib6","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1002\/jcph.735","article-title":"Renal transporter-mediated drug-drug interactions: are they clinically relevant?","volume":"56 Suppl 7","author":"Lepist","year":"2016","journal-title":"J\u00a0Clin Pharmacol"},{"issue":"9","key":"10.1016\/j.xphs.2017.04.076_bib7","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1021\/acs.molpharmaceut.6b00332","article-title":"Identification and quantitative assessment of uremic solutes as inhibitors of renal organic anion transporters, OAT1 and OAT3","volume":"13","author":"Hsueh","year":"2016","journal-title":"Mol Pharm"},{"key":"10.1016\/j.xphs.2017.04.076_bib8","series-title":"Fast Facts\u2013The National Kidney Foundation","year":"2016"},{"issue":"7","key":"10.1016\/j.xphs.2017.04.076_bib9","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.xphs.2017.04.076_bib10","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1046\/j.1523-1755.63.s84.43.x","article-title":"New insights in uremic toxins","volume":"84","author":"Vanholder","year":"2003","journal-title":"Kidney Int Suppl"},{"issue":"5","key":"10.1016\/j.xphs.2017.04.076_bib11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2133\/dmpk.20.379","article-title":"Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1","volume":"20","author":"Kimura","year":"2005","journal-title":"Drug Metab Pharmacokinet"},{"issue":"7","key":"10.1016\/j.xphs.2017.04.076_bib12","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/FPC.0b013e32832cc7e9","article-title":"Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin","volume":"19","author":"Chen","year":"2009","journal-title":"Pharmacogenet Genomics"},{"issue":"2","key":"10.1016\/j.xphs.2017.04.076_bib13","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1177\/0091270003261315","article-title":"Pharmacokinetics of intravenous, single-dose tiotropium in subjects with different degrees of renal impairment","volume":"44","author":"T\u00fcrck","year":"2004","journal-title":"J\u00a0Clin Pharmacol"},{"issue":"11","key":"10.1016\/j.xphs.2017.04.076_bib14","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1002\/j.1552-4604.1995.tb04033.x","article-title":"Kidney function and age are both predictors of pharmacokinetics of metformin","volume":"35","author":"Sambol","year":"1995","journal-title":"J\u00a0Clin Pharmacol"},{"issue":"4","key":"10.1016\/j.xphs.2017.04.076_bib15","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/BF00265853","article-title":"Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction","volume":"40","author":"Takabatake","year":"1991","journal-title":"Eur J Clin Pharmacol"},{"issue":"3","key":"10.1016\/j.xphs.2017.04.076_bib16","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00280-012-1913-z","article-title":"Pharmacokinetics of sepantronium bromide (YM155), a small-molecule suppressor of survivin, in Japanese patients with advanced solid tumors: dose proportionality and influence of renal impairment","volume":"70","author":"Aoyama","year":"2012","journal-title":"Cancer Chemother Pharmacol"},{"issue":"1","key":"10.1016\/j.xphs.2017.04.076_bib17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1046\/j.1365-2125.1998.00044.x","article-title":"Single dose pharmacokinetics of lamivudine in subjects with impaired renal function and the effect of haemodialysis","volume":"46","author":"Johnson","year":"1998","journal-title":"Br J Clin Pharmacol"},{"issue":"6","key":"10.1016\/j.xphs.2017.04.076_bib18","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1128\/AAC.40.6.1514","article-title":"Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction","volume":"40","author":"Heald","year":"1996","journal-title":"Antimicrob Agents Chemother"},{"issue":"12","key":"10.1016\/j.xphs.2017.04.076_bib25","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1002\/jcph.353","article-title":"Pharmacokinetics of renally excreted drug dexpramipexole in subjects with impaired renal function","volume":"54","author":"He","year":"2014","journal-title":"J\u00a0Clin Pharmacol"},{"key":"10.1016\/j.xphs.2017.04.076_bib26","series-title":"High Blood Pressure (Hypertension) Information | cdc.gov","year":"2016"},{"issue":"17","key":"10.1016\/j.xphs.2017.04.076_bib27","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1001\/jama.298.17.2038","article-title":"Prevalence of chronic kidney disease in the United States","volume":"298","author":"Coresh","year":"2007","journal-title":"JAMA"},{"issue":"3-4","key":"10.1016\/j.xphs.2017.04.076_bib28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1159\/000369817","article-title":"Uremic toxins and their effects on multiple organ systems","volume":"128","author":"Lisowska-Myjak","year":"2014","journal-title":"Nephron Clin Pract"},{"issue":"4","key":"10.1016\/j.xphs.2017.04.076_bib29","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1158\/1078-0432.CCR-11-2503","article-title":"Proximal tubular secretion of creatinine by organic cation transporter OCT2 in cancer patients","volume":"18","author":"Ciarimboli","year":"2012","journal-title":"Clin Cancer Res"},{"issue":"12","key":"10.1016\/j.xphs.2017.04.076_bib30","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s00424-013-1307-z","article-title":"Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter","volume":"465","author":"Schophuizen","year":"2013","journal-title":"Pflugers Arch"},{"issue":"8","key":"10.1016\/j.xphs.2017.04.076_bib31","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/j.bcp.2009.01.010","article-title":"Transport of guanidine compounds by human organic cation transporters, hOCT1 and hOCT2","volume":"77","author":"Kimura","year":"2009","journal-title":"Biochem Pharmacol"},{"issue":"13","key":"10.1016\/j.xphs.2017.04.076_bib32","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1021\/jm2001629","article-title":"Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2","volume":"54","author":"Kido","year":"2011","journal-title":"J\u00a0Med Chem"},{"issue":"9","key":"10.1016\/j.xphs.2017.04.076_bib33","doi-asserted-by":"crossref","first-page":"e0136451","DOI":"10.1371\/journal.pone.0136451","article-title":"Substrate-dependent inhibition of the human organic cation transporter OCT2: a comparison of metformin with experimental substrates","volume":"10","author":"Hacker","year":"2015","journal-title":"PLoS ONE"},{"key":"10.1016\/j.xphs.2017.04.076_bib34","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0002-9343(60)90225-4","article-title":"The pathologic physiology of chronic Bright's disease. An exposition of the \u201cintact nephron hypothesis\u201d","volume":"28","author":"Bricker","year":"1960","journal-title":"Am J Med"},{"key":"10.1016\/j.xphs.2017.04.076_bib35","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000402883","article-title":"The role of the interstitium of the renal cortex in renal disease","volume":"16","author":"Bohle","year":"1979","journal-title":"Contrib Nephrol"},{"issue":"2","key":"10.1016\/j.xphs.2017.04.076_bib36","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1046\/j.1523-1755.2002.00464.x","article-title":"Down-regulation of rat organic cation transporter rOCT2 by 5\/6 nephrectomy","volume":"62","author":"Ji","year":"2002","journal-title":"Kidney Int"},{"issue":"1","key":"10.1016\/j.xphs.2017.04.076_bib37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13550-016-0211-x","article-title":"Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease","volume":"6","author":"Pedersen","year":"2016","journal-title":"EJNMMI Res"},{"issue":"11","key":"10.1016\/j.xphs.2017.04.076_bib38","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1097\/FPC.0b013e3283559b22","article-title":"Metformin pathways: pharmacokinetics and pharmacodynamics","volume":"22","author":"Gong","year":"2012","journal-title":"Pharmacogenet Genomics"},{"issue":"6","key":"10.1016\/j.xphs.2017.04.076_bib39","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.bcp.2013.07.008","article-title":"Role of organic cation transporter OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2-K for transport and drug interactions of the antiviral lamivudine","volume":"86","author":"M\u00fcller","year":"2013","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"10.1016\/j.xphs.2017.04.076_bib40","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1021\/mp900206j","article-title":"Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation\/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption","volume":"7","author":"Nakamura","year":"2010","journal-title":"Mol Pharm"},{"issue":"2","key":"10.1016\/j.xphs.2017.04.076_bib41","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1124\/jpet.111.184986","article-title":"Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney","volume":"340","author":"Ito","year":"2012","journal-title":"J\u00a0Pharmacol Exp Ther"},{"issue":"4","key":"10.1016\/j.xphs.2017.04.076_bib42","doi-asserted-by":"crossref","first-page":"680","DOI":"10.3390\/pharmaceutics3040680","article-title":"Transporter-mediated drug-drug interactions with oral antidiabetic drugs","volume":"3","author":"Klatt","year":"2011","journal-title":"Pharmaceutics"},{"issue":"5","key":"10.1016\/j.xphs.2017.04.076_bib43","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1124\/dmd.105.008375","article-title":"Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid","volume":"34","author":"Tahara","year":"2006","journal-title":"Drug Metab Dispos"},{"issue":"3","key":"10.1016\/j.xphs.2017.04.076_bib44","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jcla.20456","article-title":"p-Cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease","volume":"25","author":"Lin","year":"2011","journal-title":"J\u00a0Clin Lab Anal"},{"issue":"9","key":"10.1016\/j.xphs.2017.04.076_bib45","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/ki.2012.290","article-title":"Competition for organic anion transporters in chronic renal disease","volume":"82","author":"Lowenstein","year":"2012","journal-title":"Kidney Int"},{"issue":"3","key":"10.1016\/j.xphs.2017.04.076_bib46","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/BF03189651","article-title":"Pharmacokinetic effects of altered plasma protein binding of drugs in renal disease","volume":"9","author":"Keller","year":"1984","journal-title":"Eur J Drug Metab Pharmacokinet"},{"issue":"5","key":"10.1016\/j.xphs.2017.04.076_bib47","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/ki.1988.99","article-title":"Drug protein binding in chronic renal failure: evaluation of nine drugs","volume":"33","author":"Vanholder","year":"1988","journal-title":"Kidney Int"},{"issue":"1","key":"10.1016\/j.xphs.2017.04.076_bib48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0378-5173(89)90159-2","article-title":"The influence of disease on plasma protein binding of drugs","volume":"54","author":"Graingerrousseau","year":"1989","journal-title":"Int J Pharm"},{"issue":"6","key":"10.1016\/j.xphs.2017.04.076_bib49","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1093\/ndt\/gfr616","article-title":"Albumin-binding capacity (ABiC) is reduced in patients with chronic kidney disease along with an accumulation of protein-bound uraemic toxins","volume":"27","author":"Klammt","year":"2012","journal-title":"Nephrol Dial Transpl"},{"issue":"4","key":"10.1016\/j.xphs.2017.04.076_bib50","doi-asserted-by":"crossref","first-page":"247","DOI":"10.7326\/0003-4819-145-4-200608150-00004","article-title":"Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate","volume":"145","author":"Levey","year":"2006","journal-title":"Ann Intern Med"},{"issue":"6","key":"10.1016\/j.xphs.2017.04.076_bib51","doi-asserted-by":"crossref","first-page":"461","DOI":"10.7326\/0003-4819-130-6-199903160-00002","article-title":"A\u00a0more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation","volume":"130","author":"Levey","year":"1999","journal-title":"Ann Intern Med"},{"issue":"1","key":"10.1016\/j.xphs.2017.04.076_bib52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1159\/000180580","article-title":"Prediction of creatinine clearance from serum creatinine","volume":"16","author":"Cockcroft","year":"1976","journal-title":"Nephron"}],"container-title":["Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354917303477?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354917303477?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,4,11]],"date-time":"2021-04-11T10:44:12Z","timestamp":1618137852000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022354917303477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["S0022354917303477"],"URL":"https:\/\/doi.org\/10.1016\/j.xphs.2017.04.076","relation":{},"ISSN":["0022-3549"],"issn-type":[{"value":"0022-3549","type":"print"}],"subject":[],"published":{"date-parts":[[2017,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The Effect of Uremic Solutes on the Organic Cation Transporter 2","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xphs.2017.04.076","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Published by Elsevier Inc. on behalf of the American Pharmacists Association.","name":"copyright","label":"Copyright"}]}}