{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:51:51Z","timestamp":1787021511633,"version":"build-2736575974"},"reference-count":10,"publisher":"SMC Media","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Background:\u00a0Certain scientific publications suggest that medications with high protein binding, such as phenytoin, have lower-than-expected serum levels in patients receiving enteral nutrition (EN) preparations or nutritional supplements. Valproic acid (VPA) is highly protein bound but currently no interactions with EN that would reduce serum levels have been documented. Case description:\u00a0A 69-year-old patient receiving enteral VPA oral solution via a nasojejunal tube experienced a clinically significant decrease in serum concentration when EN was initiated. Other sources of interactions were ruled out, and VPA serum concentration increased when doses were separated from EN by one hour. Discussion:\u00a0Interactions between highly protein bound compounds and EN have been previously described for other medications. However, there is a lack of data regarding the interaction between EN and VPA; only one published case has involved a protein supplement administered via percutaneous endoscopic gastrostomy. In our case, adjusting the timing of medication administration relative to enteral feeding resulted in increased serum VPA levels, which correlated with an improvement in clinical outcomes, suggesting the potential interaction. Conclusion:\u00a0These findings suggest a potential interaction between EN and the absorption of VPA, which may lead to reduced drug absorption and significant clinical implications.<\/jats:p>","DOI":"10.12890\/2025_005657","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T15:38:08Z","timestamp":1755531488000},"source":"Crossref","is-referenced-by-count":1,"title":["Potential pharmacokinetic interaction between enteral nutrition and valproic acid"],"prefix":"10.12890","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3874-0407","authenticated-orcid":false,"given":"Natal\u00ed Giselle","family":"Lara-Gonzalez","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Hospital Cl\u00ednico San Carlos; IdISSC, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3959-8196","authenticated-orcid":false,"given":"Iv\u00e1n Alejandro","family":"D\u00edaz-Rengifo","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Hospital Cl\u00ednico San Carlos; IdISSC, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-2958","authenticated-orcid":false,"given":"Ana Isabel","family":"Terleira Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Hospital Cl\u00ednico San Carlos; IdISSC, Madrid, Spain; Department of Pharmacology and Toxicology, Universidad Complutense; IdISSC, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6040-6403","authenticated-orcid":false,"given":"Mar\u00eda Rosario","family":"Salas-Butr\u00f3n","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Hospital Cl\u00ednico San Carlos; IdISSC, Madrid, Spain; Department of Pharmacology and Toxicology, Universidad Complutense; IdISSC, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10397","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"10.12890\/2025_005657_ref1","unstructured":"Valproic Acid Ficha T\u00e9cnica. Spanish Agency for Medicines and Medical Devices (AEMPS). Available: https:\/\/cima.aemps.es\/cima\/pdfs\/es\/ft\/48828\/FT_48828.html.pdf (In Spanish.)"},{"key":"10.12890\/2025_005657_ref2","doi-asserted-by":"crossref","unstructured":"Johannessen CU. Mechanisms of action of valproate: a commentary. Neurochem Int 2000;37:103\u2013110. doi:10.1016\/S0197-0186(00)00013-9","DOI":"10.1016\/S0197-0186(00)00013-9"},{"key":"10.12890\/2025_005657_ref3","doi-asserted-by":"crossref","unstructured":"Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 2002;16:695\u2013714. doi:10.2165\/00023210-200216100-00004","DOI":"10.2165\/00023210-200216100-00004"},{"key":"10.12890\/2025_005657_ref4","doi-asserted-by":"crossref","unstructured":"Bauer LA. Interference of oral phenytoin absorption by continuous nasogastric feedings. Neurology 1982;32:570\u2013572. doi:10.1212\/wnl.32.5.570","DOI":"10.1212\/WNL.32.5.570"},{"key":"10.12890\/2025_005657_ref5","doi-asserted-by":"crossref","unstructured":"Hamilton RA, Garnett WR, Kline BJ, Pellock JM. Effects of food on valproic acid absorption. Am J Hosp Pharm 1981;38:1490\u20131493.","DOI":"10.1093\/ajhp\/38.10.1490"},{"key":"10.12890\/2025_005657_ref6","doi-asserted-by":"crossref","unstructured":"VandenBerg A, Broadway J. Enteral administration of protein supplement and valproate: a potential pharmacokinetic interaction. Ment Health Clin 2018;7:10\u201312. doi:10.9740\/mhc.2017.01.010","DOI":"10.9740\/mhc.2017.01.010"},{"key":"10.12890\/2025_005657_ref7","doi-asserted-by":"crossref","unstructured":"Hennessy DD. Recovery of phenytoin from feeding formulas and protein mixtures. Am J Health Syst Pharm 2003;60:1850\u20131852. doi: 10.1093\/ajhp\/60.18.1850","DOI":"10.1093\/ajhp\/60.18.1850"},{"key":"10.12890\/2025_005657_ref8","doi-asserted-by":"crossref","unstructured":"Au Yeung SC, Ensom MH. Phenytoin and enteral feedings: does evidence support an interaction? Ann Pharmacother 2000;34:896\u2013905. doi:10.1345\/aph.19355","DOI":"10.1345\/1542-6270(2000)034<0896:PAEFDE>2.0.CO;2"},{"key":"10.12890\/2025_005657_ref9","doi-asserted-by":"crossref","unstructured":"Webb AJ, Avramovska S, Qualls S, Lo CK, Roberts RJ, Barra ME. Impact of an enteral nutrition holding guideline on daily nutrition goals in patients taking phenytoin. Nutr Clin Pract 2023;38:1334\u20131342. doi:10.1002\/ncp.11051","DOI":"10.1002\/ncp.11051"},{"key":"10.12890\/2025_005657_ref10","doi-asserted-by":"crossref","unstructured":"Williams NT. Medication administration through enteral feeding tubes. Am J Health Syst Pharm 2008;65:2347\u20132357. doi:10.2146\/ajhp080155","DOI":"10.2146\/ajhp080155"}],"container-title":["European Journal of Case Reports in Internal Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.ejcrim.com\/index.php\/EJCRIM\/article\/download\/5657\/4789","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ejcrim.com\/index.php\/EJCRIM\/article\/download\/5657\/4790","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ejcrim.com\/index.php\/EJCRIM\/article\/download\/5657\/4790","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T12:44:08Z","timestamp":1756903448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ejcrim.com\/index.php\/EJCRIM\/article\/view\/5657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":10,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.12890\/2025_005657","relation":{"has-manifestation":[{"id-type":"other","id":"1-129-5657-g4789","asserted-by":"subject"},{"id-type":"other","id":"1-129-5657-g4790","asserted-by":"subject"}],"is-part-of":[{"id-type":"other","id":"1-129","asserted-by":"subject"}]},"ISSN":["2284-2594"],"issn-type":[{"value":"2284-2594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,18]]}}}