Pharmacokinetics of carbamazepine in the dog.

1. The pharmacokinetics of carbamazepine was studied in dogs after oral administration of two pharmaceutical preparations. Adsorption was rapid, however, the drug was much better absorbed from a liquid preparation than from tablets. Plasma concentrations declined with an elimination half-life of 1.5 hr. Carbamazepine-10,11-epoxide, which is equipotent with carbamazepine as an anticonvulsant, was rapidly formed and reached plasma concentrations higher than those of the mother compound. The concentrations of the epoxide remained high as long as plasma concentrations of carbamazepine were above 2--4 nmole/ml, then they fell with an average half-life of 2.2 hr. 2. During continued treatment with daily doses of 0.34--0.38 mmole/kg carbamazepine, plasma concentrations showed a pronounced and progressive decline from Day 2 which is considered as the result of induction of microsomal liver enzymes. 3. Carbamazepine and the epoxide pass into CSF at a rate comparable to that of phenobarbital or barbital and primidone, respectively. 4. Binding to serum proteins was about 70% for carbamazepine and 40% for the epoxide in dog serum; slightly higher values were found for human serum.