Meal-dependent absorption of enteric-coated sodium valproate

Area of Science:

• Pharmacokinetics
• Drug Absorption
• Gastroenterology

Background:

• Valproic acid (VPA) is a widely used antiepileptic drug.
• Enteric-coated (EC) formulations are designed to delay drug release until the small intestine.
• The impact of food on VPA absorption from EC formulations requires clarification.

Purpose of the Study:

• To investigate the effect of meals on the absorption of enteric-coated valproic acid (VPA).
• To determine if food intake alters the rate or extent of VPA absorption from an EC formulation.

Main Methods:

• Study I: Healthy volunteers received 500 mg EC VPA under fasting, fed, or 3-hour post-meal conditions.
• Study II: Volunteers received intravenous VPA and EC VPA 3 hours post-meal for bioavailability assessment.
• Blood samples were analyzed for VPA concentrations to determine pharmacokinetic parameters.

Main Results:

• Food intake significantly prolonged the latency period (Lp) for VPA absorption (fasting: 1.67 hr; fed: 6.75 hr; 3-hr post-meal: 7.63 hr).
• Bioavailability of EC VPA was 100% when administered 3 hours after a meal.
• Intravenous VPA pharmacokinetic parameters (clearance, volume of distribution, half-life) were consistent with literature values.

Conclusions:

• Food intake delays the absorption of valproic acid from enteric-coated formulations.
• The extent of valproic acid absorption is not significantly decreased by food.
• Administration timing relative to meals may influence the onset of therapeutic effect for EC VPA.