Effect of the timing of food intake on the absorption and bioavailability of carbamazepine immediate-release tablets in beagle dogs.

The effect of dosing time on the bioavailability of carbamazepine immediate-release (IR) tablets was investigated when administered to beagle dogs who were fasting, with co-administration of food (Co-food), and 0.5 h before food and 2 h after food. The study was conducted using a single dose of 200 mg (tablets/solution) with a 2 week washout period in a crossover design. Food intake significantly increased the rate and extent of tablet absorption. The C(max) (µg·ml⁻¹, 8.13/3.65) and t(max) (h, 1.83/0.92) were increased more than two-fold and the AUC₀₋₂₄ (µg·h·ml⁻¹, 20.09/8.19) was 2.5 times that of the values obtained under fasting conditions. The bioavailability of the tablets under fasting conditions was 91.2%, but increased to 223.5%, 182.8% and 148.4% in the Co-food, 0.5 h before food and 2 h after food groups, respectively (p < 0.05). Although there was no significant difference in the C(max) or AUC₀₋₂₄ between the treatments with food, the absorption appeared to be reduced to some extent when the tablets were given 2 h after food. The oral bioavailability of CBZ IR tablets was significantly affected by the timing of the food intake. This is maybe favored by the fluctuations in the level of bile salts with the timing of food intake. To obtain acute therapy for a drug with narrow therapeutic window, attention should be given to the dosing time and food intake interactions.