Lara-Gonzalez Natalí Giselle, Díaz-Rengifo Iván Alejandro, Terleira-Fernández Ana Isabel, Salas-Butrón María Rosario
Department of Clinical Pharmacology, Hospital Clínico San Carlos; IdISSC, Madrid, Spain.
Department of Pharmacology and Toxicology, Universidad Complutense; IdISSC, Madrid, Spain.
Eur J Case Rep Intern Med. 2025 Aug 18;12(9):005657. doi: 10.12890/2025_005657. eCollection 2025.
Certain 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.
A 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.
Interactions 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.
These findings suggest a potential interaction between EN and the absorption of VPA, which may lead to reduced drug absorption and significant clinical implications.
Enteral nutrition may reduce the absorption of valproic acid. This could potentially result in subtherapeutic serum levels and worsen clinical outcomes.Clinicians should closely monitor serum levels and consider separating the administration of valproic acid and enteral nutrition by at least one hour.
某些科学出版物表明,蛋白结合率高的药物,如苯妥英钠,在接受肠内营养(EN)制剂或营养补充剂的患者中血清水平低于预期。丙戊酸(VPA)蛋白结合率高,但目前尚无与EN相互作用导致血清水平降低的文献记载。
一名69岁患者通过鼻空肠管接受肠内VPA口服溶液治疗,开始肠内营养时血清浓度出现了具有临床意义的下降。排除了其他相互作用来源,当药物剂量与肠内营养间隔一小时给药时,VPA血清浓度升高。
之前已有其他药物的高蛋白结合化合物与肠内营养相互作用的描述。然而,关于肠内营养与VPA之间的相互作用缺乏数据;仅有一篇发表的病例涉及经皮内镜下胃造口术给予的蛋白质补充剂。在我们的病例中,调整药物给药时间与肠内喂养的相对时间,导致VPA血清水平升高,这与临床结果的改善相关,提示存在潜在相互作用。
这些发现提示肠内营养与VPA吸收之间可能存在相互作用,这可能导致药物吸收减少并具有重大临床意义。
肠内营养可能会降低丙戊酸的吸收。这可能会导致血清水平低于治疗浓度并使临床结果恶化。临床医生应密切监测血清水平,并考虑将丙戊酸和肠内营养的给药时间至少间隔一小时。