ORAL PHARMACOKINETICS OF CARBAMAZEPINE IN DOGS FROM COMMERCIAL TABLETS AND A CYCLODEXTRIN COMPLEX

The extent of absorption of carbamazepine from a 2-hydroxypropyl-beta-cyclodextrin/carbamazepine complex was significantly greater and the rate of absorption was faster when compared with an immediate-release carbamazepine tablet in the dog. Six dogs were dosed orally in a two-way crossover study in which the tablet was compared with an equivalent dose of the complex in solution. The area under the curve of concentration versus time for the complex was 5.6 times greater than the tablet, whereas the mean time to reach maximum concentration for the tablet was 1.4 hours versus 0.5 hours for the complex. The complex, therefore, had a greater rate and extent of absorption. A rapidly acting and better absorbed carbamazepine product has the potential to decrease the daily dose of carbamazepine, increase its utility as emergency treatment of epileptic seizures, and provide an acceptable alternative dosage form in patients who are unable to swallow tablets.