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Uremic toxins accumulate in patients with CKD and significantly impact drug pharmacokinetics and drug responses. These toxins modify drug pharmacokinetics. Indeed, uremic toxins can alter intestinal absorption by affecting drug transporters, such as P\u2010glycoprotein and multidrug resistance\u2013associated proteins. These changes modify the bioavailability of drugs and change drug absorption profiles in patients with CKD. Furthermore, uremic toxins interfere with drug distribution and metabolism. For instance, the urea\u2010driven carbamylation of albumin can reduce drug\u2010binding sites on this plasma protein and thus increase the free drug fraction. In the liver, CKD can reduce the expression of cytochrome P450 enzymes and thus impair drug biotransformation. Furthermore, uremic toxins can interact with cellular transporters, affecting drug clearance and leading to drug accumulation. In terms of pharmacodynamics, uremic toxins can alter receptor function and impair drug effectiveness. The blood\u2013brain barrier may also be disrupted by the accumulation of toxins; this enhances drug penetration into the brain and increases the risk of adverse effects. After providing a brief summary of the various drug elimination pathways and the definitions and classification of uremic toxins, we shall use examples to illustrate the potential impact of a decrease in glomerular filtration rate (GFR) and\/or an increase in uremic toxin levels on drug pharmacokinetics and pharmacodynamics.<\/jats:p>","DOI":"10.1111\/fcp.70037","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T05:59:31Z","timestamp":1752904771000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Drug Exposure in Chronic Kidney Disease: It Is Not Just About the Glomerular Filtration Rate"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5384-9006","authenticated-orcid":false,"given":"Sophie","family":"Liabeuf","sequence":"first","affiliation":[{"name":"Pharmacoepidemiology Unit, Department of Clinical Pharmacology Amiens\u2010Picardie University Hospital  Amiens France"},{"name":"MP3CV Laboratory Jules Verne University of Picardie  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Berdougo\u2010Tritz","sequence":"additional","affiliation":[{"name":"GPR  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Augey","sequence":"additional","affiliation":[{"name":"GPR  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A\u00efcha","family":"Mbarek","sequence":"additional","affiliation":[{"name":"GPR  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-7812","authenticated-orcid":false,"given":"Michel","family":"Jadoul","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Cliniques Universitaires Saint\u2010Luc Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Deray","sequence":"additional","affiliation":[{"name":"GPR  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad\u00a0A.","family":"Massy","sequence":"additional","affiliation":[{"name":"INSERM Unit 1018, Team 5, CESP H\u00f4pital Paul Brousse, Paris\u2010Saclay University (UPS) and Versailles Saint\u2010Quentin\u2010en\u2010Yvelines University (UVSQ)  Villejuif France"},{"name":"AURA (Association Pour L'utilisation du Rein Artificiel Dans la r\u00e9gion Parisienne)  Paris France"},{"name":"Department of Nephrology Ambroise Par\u00e9 University Hospital (APHP)  Boulogne\u2010Billancourt\/Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04041206"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)31694\u20105"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)32225\u20106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.11.003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012040392"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.4852"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2023.09.012"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b20\u201000929"},{"key":"e_1_2_10_10_1","unstructured":"Giotrif|European Medicines Agency (EMA). 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