Effect of cholestyramine resin on single dose valproate pharmacokinetics.

Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine the effect of cholestyramine on the plasma concentrations of valproic acid (VPA) following concurrent and staggered (VPA 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. In each phase fasting subjects received 250 mg of VPA followed by serial blood sampling for VPA plasma concentrations over a 37-hour period. In the concurrent and staggered phase the subjects received 4 g of cholestyramine (CHOL) twice daily 24 hours prior to and following the VPA dose. During the concurrent phase the coadministration of CHOL resulted in a decrease (p < 0.05) in the area under the curve (AUC) for VPA compared to VPA alone (415.2 +/- 113.2 mghr/l vs 489.2 +/- 153.0 mghr/l, respectively). When the same dose of each drug was administered 3 hours apart, the AUC for VPA (454.8 +/- 123.1 mghr/l) was not significantly decreased when compared to VPA alone (489.2 +/- 153.0 mghr/l). Also, the bioavailability relative to VPA alone was 86.2% +/- 7.1 for the concurrent phase and 95.3% +/- 13.6 for the staggered phase. Based on the AUC of VPA concurrent administration of CHOL significantly decreases VPA absorption and separating the doses of the 2 drugs by 3 hours may lessen the interaction.