Steady-state bioequivalence studies of two memantine tablet and oral solution formulations in healthy volunteers

The bioavailability of memantine was compared using two tablet (Memantine LACHEMA 10 tbl. obd. and Akatinol® Memantine 10 tbl. obd., Study A) and two oral solution formulations (Memantine LACHEMA gtt. and Akatinol® Memantine gtt., Study B) containing 10 mg memantine hydrochloride in two randomized, two-period, two-sequence, crossover studies with 24 healthy volunteers. In both study periods, memantine concentrations were determined by gas-chromatography with electron-capture detection in plasma samples taken at the steady state after 22 days of once-daily dosing. The arithmetic mean (SD) pharmacokinetic parameters in the studies A and B were: AUC0-0τ,ss 768 (141) vs. 727 (99) and 807 (154) vs. 836 (156) ng/ml h, Cmax,ss 37.3 (6.1) vs. 35.2 (4.5) and 39.2 (7.3) vs. 40.6 (6.7) ng/ml. Median values of Tmax were in the range of 4 to 5 h. Both tablet and oral solution formulations were found bioequivalent (90%-confidence intervals for AUC0-τ,ss, Cmax,ss and Cτ,ss within 101-114% (Study A) and 92 and 104% (Study B)). For the peak-trough fluctuation, the bioequivalence intervals were 85-107% and 86-04%, respectively. By pooled analysis of both studies, the geometric mean (90% CI) relative bioavailability of memantine from tablets compared to oral solutions was 91% (85-98).