Summary: 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, crossover 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. Key Words: Carbamazepine-PharmacokineticsExtended release-Epilepsy.Since its first introduction into clinical use for the treatment of epilepsy in the 1970s (1-3), carbamazepine (CBZ) has become a drug of choice for the treatment of simple partial, complex partial, and secondarily generalized tonic-clonic seizures (SPS, CPS, SGTCS). The conventional immediate-release forms of CBZ, require frequent (three or four times daily) dosing, however, and variability in CBZ drug levels in the blood has been reported. Both of these issues are problematic (4-6).Adherence to a medication regimen is a major issue in the pharmacological treatment of epilepsy, with studies frequently linking seizures to poor adherence. Adherence can be affected by both the frequency of drug administration as well as the occurrence of side effects, frequently linked to blood levels of drug. Additional factors affecting adherence to a regimen by patients with epilepsy may be memory difficulties and frequent seizures. In studies from several centers, adherence to antiepileptic drug (AED) dosing regimens ranged from 39 to 82% (7)(8)(9)(10)(11). In a study of patients with epilepsy using electronic compliance monitors, adherence to a once-or twice-daily regimen was -80%, as contrasted with -40% adherence to a four-times-daily regimen (12). A patient's variable adherence to an AED regimen can lead to increased variability in blood levels (1 3). One of the issues involved in the dosing of CBZ is its high degree of insolubility and variations in bioavailability. Peak-to-trough fluctu...