Enteral administration of protein supplement and valproate: A potential pharmacokinetic interaction

Valproic acid (VPA) and its derivatives are highly protein bound. Certain highly protein bound medications (eg, phenytoin) have specific administration instructions for patients on enteral nutrition supplements to optimize absorption of the medication. Pharmacokinetic interactions between VPA and enteral nutrition or protein supplements demonstrating impaired absorption have not been published to date.

A patient receiving enteral VPA syrup via percutaneous endoscopic gastrostomy tube experienced a clinically significant decrease in serum concentration when enteral protein supplement was initiated. Other sources of interactions were ruled out, and VPA serum concentration increased when doses were separated from protein supplement by 2 hours.

This is the first published case of enteral protein supplementation affecting absorption of enteral VPA. Enteral feeds are known to interact with other highly protein bound medications, and clinical practice for these medications may be used to guide administration when an interaction with VPA is suspected.

When using enteral protein supplements concomitantly with enteral VPA, clinicians may consider separating doses to avoid potential interaction or impaired absorption.