Bioequivalence of Intravenous and Oral Formulations of the Antiepileptic Drug Lacosamide

Abstract

Background/Aims: To evaluate the bioequivalence of intravenous and oral lacosamide (tablet), an antiepileptic drug. Methods: Two randomized, single-dose (200 mg) trials were conducted: a 2-way trial (study A, 15-min infusion, oral tablet) and a 3-way crossover trial (study B, 30- and 60-min infusions, oral tablet). Twenty four healthy men participated in study A and 27 in study B. Eighteen blood samples were taken before to 72 h after lacosamide administration during each treatment period, followed by a 1-week washout. Safety and the ratio of intravenous/oral lacosamide for AUC_0–tz (area under the concentration-time curve from zero up to the last measurable plasma concentration) and C_max (maximum plasma concentration) were evaluated. Results: For AUC_0–tz and C_max, 90% confidence intervals for the ratio of intravenous/oral lacosamide fell within the predetermined bioequivalence range (80–125%) for 30- and 60-min infusions. In study A, all adverse events (AEs) were mild, with no discontinuations. In study B, 3 volunteers discontinued due to AEs; one serious AE (epiglottitis) was reported. No clinically relevant effects on vital signs, electrocardiograms or laboratory parameters and no AEs relating to infusion site were reported. Conclusion: Intravenous infusions (15, 30 and 60 min) of 200 mg lacosamide are as well tolerated as the oral tablet. Bioequivalence was demonstrated for 30- and 60-min infusions; therefore, direct conversion from oral to intravenous lacosamide, or vice versa, is possible.