{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:34:25Z","timestamp":1791646465498,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Equations to calculate albumin\u2010adjusted total concentrations have been validated to correlate with measured free concentrations for both phenytoin and valproate, but there is a lack of data to assess correlation with clinical outcomes. We aimed to assess the association of hypoalbuminaemia and albumin\u2010adjusted total concentrations with concentration\u2010dependent toxicity for phenytoin and valproate and review the impact on management decisions following concentration monitoring in hypoalbuminaemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients undergoing concentration monitoring for phenytoin or valproate between January and December 2018 were included. Patients were identified using a centralised laboratory database with data extracted from medical records.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total phenytoin concentrations were measured for 144 patients, with hypoalbuminaemia (\u226430\u2009g\u2009L<jats:sup>\u22121<\/jats:sup>) recorded in 59 (41%) patients. Albumin\u2010adjusted phenytoin concentration &gt;20\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup> was associated with increased neurological adverse effects (77% <jats:italic>vs<\/jats:italic>. 43%, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). On logistic regression, higher albumin\u2010adjusted phenytoin concentration was an independent risk factor for neurotoxicity (OR 1.06, 95% CI 1.01\u20131.12, <jats:italic>P<\/jats:italic>\u2009=\u2009.011). Total valproate concentrations were measured for 383 patients, with hypoalbuminaemia (\u226430\u2009g\u2009L<jats:sup>\u22121<\/jats:sup>) noted in 53 (14%) patients. For the valproate cohort, hypoalbuminaemia (42% <jats:italic>vs<\/jats:italic>. 28%, <jats:italic>P<\/jats:italic>\u2009=\u2009.039) and albumin\u2010adjusted valproate concentration &gt;100\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup> (49% <jats:italic>vs<\/jats:italic>. 23%, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001) were both associated with increased neurotoxicity. On multiple logistic\u2010regression, valproate daily dose (aOR\u2009=\u20091.01, 95% CI 1.00\u20131.02, <jats:italic>P<\/jats:italic>\u2009=\u2009.006) and albumin\u2010adjusted valproate concentration (aOR 1.01, 95% CI 1.00\u20131.02, <jats:italic>P<\/jats:italic>\u2009=\u2009.033) were independent risk factors for neurotoxicity after accounting for confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>While measuring free drug concentrations in hypoalbuminaemia would be ideal, the adjustment equations can help identify vulnerable patients needing further assessment of potential concentration\u2010dependent toxicity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14853","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T14:00:35Z","timestamp":1617976835000},"page":"4341-4353","source":"Crossref","is-referenced-by-count":7,"title":["Monitoring for valproate and phenytoin toxicity in hypoalbuminaemia: A retrospective cohort study"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9412-0681","authenticated-orcid":false,"given":"Arushi","family":"Madan","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Royal Brisbane &amp; 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Women's Hospital  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000546"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.5694\/mja17.00951"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2006.08.026"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/9781108669399"},{"key":"e_1_2_10_6_1","volume-title":"Australian Medicines Handbook","year":"2019"},{"key":"e_1_2_10_7_1","volume-title":"MIMS Online","year":"2019"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2014.0714"},{"key":"e_1_2_10_9_1","volume-title":"Toxicology Handbook","author":"Murray L","year":"2015"},{"key":"e_1_2_10_10_1","volume-title":"Toxinz Poisons Information"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.2269"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200502000-00004"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2014.0704"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.8.6.929"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1994.tb04304.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.105.2.602"},{"key":"e_1_2_10_17_1","volume-title":"Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring","author":"Tozer TN","year":"1992"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FPE04007X"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e3283374e3c"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028016628166"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6947-12-7"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1965"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-018-0627-4"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70153-9"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0406-8"},{"key":"e_1_2_10_26_1","first-page":"45","article-title":"Determinants of health\u2010related quality of life in pharmacoresistant epilepsy: results from a large multicentre study of consecutively enrolled patients using validated quantitative assessments","volume":"94","author":"Luoni C","year":"2011","journal-title":"Epilepsia"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-007-9043-9"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12884"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7139.1236"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199001000-00010"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.62.1.23"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02713.x"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14853","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.14853","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14853","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T09:12:03Z","timestamp":1693213923000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.14853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":31,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/bcp.14853"],"URL":"https:\/\/doi.org\/10.1111\/bcp.14853","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]}}}