Bioequivalence of intravenous and oral formulations of the antiepileptic drug lacosamide.
OBJECTIVE
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.


CONCLUSIONS
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.
UCB Pharma, Monheim, Germany. Willi.Cawello@ucb.com
Willi
W
Cawello
Rainer
R
Bonn
Hilmar
H
Boekens
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D006801:Humans; D007262:Infusions, Intravenous; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency; D055815:Young Adult
D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide