Pharmacokinetic Evaluation of Twice‐Daily Extended‐Release Carbamazepine (CBZ) and Four‐Times‐Daily Immediate‐Release CBZ in Patients with Epilepsy

Purpose: A new capsule dosage form of carbamazepine (CBZ) has been developed, consisting of three different types of beads (immediate‐release, extended‐release, and enteric‐release) that may be taken sprinkled on food or swallowed for easy administration. We compared the pharmacokinetics of the extended‐release dosage form of CBZ (Carbatrol capsules) twice daily with the conventional immediate‐release formulation of CBZ four times daily. Methods: The randomized, double‐blind, two‐way, cross‐over study was conducted at two sites, with a planned sample size of 24 adult patients with epilepsy. Each treatment was administered for 2 weeks. At the end of the 2‐week period, blood samples were obtained hourly for a 24‐h period. Results: The 90% confidence intervals (CI) of the ratio of the means of the extended‐release formulation twice daily to the immediate‐release formulation four times daily were within the range of 0.80–1.25 for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ and CBZ‐epoxide (CBZ‐E). There was no difference in the frequency of seizures between treatment (p = 0.103). Conclusions: Our results demonstrate that extended‐release CBZ twice daily was bioequivalent to immediate‐release CBZ four times daily, with regard to CBZ levels and summation of CBZ and CBZ‐E levels, based on the pharmacokinetic parameters evaluated. Substituting one formulation for the other did not cause patients to have a significant change in seizure frequency.