Gabapentin absorption: effect of mixing with foods of varying macronutrient composition

To compare the oral absorption profile of gabapentin following administration of the contents of opened capsules that were mixed with food vehicles of varied macronutrient (protein) composition.

An unblinded, randomized, single-dose, four-way crossover pharmacokinetic study in nine healthy adult men and women volunteers.

Following an overnight fast, a single 600-mg dose of gabapentin (2 x 300-mg Neurontin capsules) was given either as an intact capsule swallowed with 120 mL of tap water (control, phase I), or after capsule contents were opened and mixed with; 4 oz. of applesauce (phase II), 120 mL of orange juice (phase III), or 4 oz. of fat-free chocolate pudding (phase IV). Subjects fasted for 4 hours following drug ingestion. Serial venous blood samples were obtained over 24 hours to determine gabapentin serum concentrations. Pharmacokinetic variables including AUC, maximum serum concentration (Cmax), and time to maximum serum concentration (tmax) were calculated by using standard noncompartmental methods. Subjects served as their own controls, and were randomly crossed over following a minimum 7-day washout period. Statistical analysis was performed by using ANOVA and Student's t-test where appropriate.

No statistically significant differences in any kinetic variable were found between any study arm. A trend was noted for a modest increase in both Cmax and AUC in phase IV (chocolate pudding) compared with control (+18.6% and +13.2%, respectively). In a comparison of protein (phase IV) versus nonprotein phases (phases I-III), gabapentin AUC was 26% greater (47.28+/-14.65 vs. 37.43+/-9.78 microg/mL x h; p = 0.03), and Cmax was 32% higher (4.72+/-1.04 vs. 3.56+/-0.92 microg/mL; p = 0.003).

Opening and mixing the contents of gabapentin capsules does not significantly impair drug absorption. This may be a viable administration option for patients who are unable to swallow intact capsules. Dietary macronutrient composition (i.e., protein) may favorably influence gabapentin oral absorption.