Abstracts

Rationale: Young patients who are unable to swallow whole tablets often receive their medication as a crushed tablet mixed with applesauce. The bioavailability of clobazam (CLB) administered as a single 20 mg dose in applesauce or fasted as the intact tablet was determined in healthy adult volunteers in a 2-way crossover design study. Methods: Group 1 received 4x5mg tablets intact and crushed in applesauce and Group 2 received 1x20mg tablet intact and crushed in applesauce. Serial blood samples were collected over 216 hours post dose for the determination of plasma concentrations of CLB and its major active metabolite N-desmethylclobazam (N-CLB) with a validated LC/MS/MS assay. Results: The ratios of crushed tablet(s) in applesauce to intact tablet(s) (90% Confidence Intervals - CI) for Cmax and AUC0-inf of CLB were 0.99 (0.90, 1.10) and 1.02 (0.97, 1.09), respectively, for Group 1 and 0.96 (0.86, 1.07) and 0.99 (0.93, 1.04), respectively, for Group 2. Ratios (90% CIs) for N-CLB were 1.03 (0.96, 1.11) and 1.02 (0.96, 1.09) for Cmax and AUC0-inf respectively for Group 1 and 0.94 (0.86, 1.03) and 0.997 (0.96, 1.04) respectively for Group 2. The most common adverse event was somnolence and the safety profile was similar between all groups. Conclusions: Therefore, CLB tablets can be administered crushed and mixed with applesauce without significant changes to the pharmacokinetic parameters.