Dietary protein interference with phenytoin release

Phenytoin is administered through feeding tubes to treat patients who cannot tolerate oral administration. Both the crushed tablet and suspension formulation are administered by this route. Many case reports have noted that phenytoin serum values drop significantly when the medication is co-administered with enteral nutrition formula. This thesis was designed to resolve some of the issues associated with this interaction.; The original thesis proposal assumed that the phenytoin-nutrient interaction was caused by protein binding to nutrients included in the feeding tube formula. The studies of this thesis, however, found that the principle issue is the change in the phenytoin release in the gastric and intestinal fluids. In the gastric fluid, the release from solid formulation is acutely sensitive to the presence of nutrition formulas. This is less the case with intestinal fluids, where phenytoin solubility is higher. This thesis also concludes that the excipients used in the tablet and suspension formulation play a crucial role in phenytoin release. Studies done using only the chemical grade powder form of phenytoin did not exhibit the dependency on nutrients to change phenytoin release parameters.; This thesis also examined the issue of phenytoin binding to the plastic of feeding tubes. Dialysis studies document that the plastic enhances phenytoin release into solution, but that no direct binding occurs. The suspension formulation contains excipients, which enhance adherence and flow through narrow bore feeding tubes. The viscosity of the suspension formulation also contributes to reduce the drug release when in a concentrated state.; This study found that the phenytoin-nutrient interaction could be minimized by diluting the suspension form to 2-3 times the original volume. The tablet release from solid, when prepared at some dilution as the concentrated suspension, did not change significantly when combined with nutrients.; This thesis identified the components of the phenytoin-nutrient interaction, which contribute significantly to the reduction in phenytoin release from solid. Calcium caseinate, a protein used in enteral feeding formulas, exhibited the same degree of interaction as the complete formula when combined with phenytoin suspension.; Future clinical studies will utilize the concepts of this report to improve patient outcome when phenytoin must be co-administered with nutrients.