Potential Pharmacokinetic Interaction Between Enteral Nutrition and Valproic Acid

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.