Bioequivalence of perampanel fine granules and tablets in healthy Japanese subjects.

OBJECTIVE: Perampanel is an approved anti-seizure drug. A new formulation of perampanel fine granules (FG; 1% perampanel) has been developed for patients who are unable to take tablets. Bioequivalence between the 4-mg FG and tablet perampanel formulations, as well as their safety and tolerability, were assessed. MATERIALS AND METHODS: In this phase I, single-center, open-label, 2-period, 2-sequence, crossover, bioequivalence study (NCT03399734), healthy Japanese subjects were randomized to receive single doses of the 4-mg FG perampanel and 4-mg perampanel tablet (separated by a ≥ 6-week washout period). Plasma samples for perampanel concentration analysis were collected pre-dose and at intervals up to 168 hours post-dose. The maximum observed concentration (Cmax) and area under the concentration-time curve from time zero to 168 hours (AUC(0-168h)) were used to assess the bioequivalence of the two formulations. RESULTS: The 90% confidence intervals (CIs) for the geometric mean ratio of test/reference for Cmax and AUC(0-168h) were within the bioequivalence criteria of 80 - 125% (Cmax 90% CI 90.8%, 110%; AUC(0-168h) 90% CI 98.2%, 112%; N = 21). 10/24 (41.7%) subjects with FG experienced ≥ 1 treatment-emergent adverse event (TEAE). The events were mild in severity and resolved within 4 hours of onset. There were no deaths, severe TEAEs, serious AEs, or TEAEs leading to study-drug withdrawal. CONCLUSION: Bioequivalence of 4-mg FG and 4-mg tablet of perampanel was demonstrated. Both perampanel formulations were generally safe and well tolerated. These data suggest that perampanel FG may be a suitable alternative formulation for patients with epilepsy who have difficulties taking perampanel tablets.

Computed tomography appearances of bronchogenic carcinoma associated with bullous lung disease.

Bullous lung disease is known to be a risk factor for developing a bronchogenic carcinoma. In this article, computed tomography appearances of 20 patients with histologically proven bronchogenic carcinoma were reviewed retrospectively. On the basis of the previous literatures and our findings, the computed tomography appearances of bronchogenic carcinoma associated with bullous lung disease could be classified into 3 types; nodule or mass extruding from the bullous wall, nodule or mass confined within the bullous lumen, and soft-tissue density extending along the bullous wall. Attention should be paid in the interpretations for mass or nodule in the wall of the bulla because they frequently lack the characteristic appearances of bronchogenic carcinoma.