Abstracts

RATIONALE: Oxcarbazepine (OXC) is an antiepileptic drug (AED) used in many countries worldwide. Three different film-coated tablet strengths are available (150, 300 and 600 mg). However, the administration of tablets to children and the elderly is sometimes troublesome. Therefore, a new oral OXC oral suspension has been developed which does not show discoloration or increased viscosity over time. A single-center, open-label trial was performed to support switching patients from the film-coated tablet to the oral suspension and vice-versa.
METHODS: Healthy male volunteers, age 18-50 years, were randomized to one of two OXC treatment groups (oral suspension 6% or 600 mg film-coated tablets) in a crossover design. During each treatment period, a single OXC 600 mg dose was administered in the am on Day 1 to determine single-dose pharmacokinetics (PK) over the next 72 hours. On Day 4 a second dose was administered in the am, and thereafter every 12 hours until the final dose on the morning of Day 8 to determine steady-state PK over the next 12 hours. Both single dose and steady-state PK were done under fasted conditions. MHD concentrations were determined by HPLC. Pharmacokinetic variables determined by model independent analysis included: AUC [h([mu]mol/L)], Cmax [[mu]mol/L], and tmax [h]. Log-transformed AUC values and Cmax of the different formulations were compared by means of the 90% Confidence Interval (CI).
RESULTS: Twenty subjects were enrolled: 17 subjects received film-coated tablets and 15 received the oral suspension. At steady-state, the oral suspension was equivalent to the film-coated tablet with regard to AUC and Cmax. The AUC and Cmax ratio of means were 1.02 (CI: 0.99, 1.06) and 1.01 (CI: 0.95, 1.06), respectively. At single dose, the oral suspension was equivalent to the film-coated tablets with respect to AUC (ratio: 0.93; CI: 0.90, 0.97). In terms of Cmax at single dose, the ratio of means for the oral suspension and the film-coated tablets was 0.77 (CI: 0.72, 0.82). Single dose pharmacokinetic data, however, is not clinically relevant in epilepsy patients who receive chronic treatment with AEDs. Therefore, multiple dose pharmacokinetics were performed. The most common adverse events were dizziness, headache, and nausea. There were no clinically relevant changes in vital signs or ECG parameters.
CONCLUSIONS: This study shows that the new oral suspension and the film-coated tablets of OXC are bioequivalent at steady-state. Furthermore, this study confirms that patients can be switched from the film-coated tablets to the new oral suspension formulation of OXC.
[Supported by: Novartis Pharmaceuticals.]; (Disclosure: Salary - Drs DSouza and Flesch - Novartis, Consulting - Dr Levisohn -Novartis, Honoraria - Levisohn - Novartis Pharmaceuticals)