J Appl Biomed 6:39-45, 2008 | DOI: 10.32725/jab.2008.006

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

Jaroslav Chládek^1,*, Bořek Žaludek², Petr Sova², Aleš Franc², Luděk Šišpera¹, Jiřina Martínková¹, Stanislav Mičuda¹, Jolana Cermanová¹

¹ Department of Pharmacology, Faculty of Medicine, Charles University, Hradec Králové, Czech Republic,

² Pliva-LACHEMA a.s., Brno, Czech Republic

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: AUC_0-0τ,ss 768 (141) vs. 727 (99) and 807 (154) vs. 836 (156) ng/ml h, C_max,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 T_max were in the range of 4 to 5 h. Both tablet and oral solution formulations were found bioequivalent (90%-confidence intervals for AUC_0-τ,ss, C_max,ss and C_τ,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).

Keywords: memantine; pharmacokinetics; bioequivalence

Received: September 11, 2007; Revised: October 4, 2007; Published: March 31, 2008  Show citation