Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 6 (2008), No 1, p 39-45




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

Jaroslav Chladek, Borek Zaludek, Petr Sova, Ales Franc, Ludek Sispera, Jirina Martinkova, Stanislav Micuda, Jolana Cermanova

Address: Jaroslav Chladek, Department of Pharmacology, Faculty of Medicine, Charles University, Simkova 870, 500 01 Hradec Kralové, Czech Republic
chladekj@lfhk.cuni.cz

Received 11th September 2007.
Revised 4th October 2007.
Published online 22nd November 2008.

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SUMMARY
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: AUC0-0t,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-t,ss, Cmax,ss and Ct,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).

KEY WORDS
memantine; pharmacokinetics; bioequivalence


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