Abstracts

Lacosamide (LCM, formerly harkoseride) belongs to a novel class of functionalized amino acids with anticonvulsant activity. Oral LCM is rapidly and completely absorbed. The peak plasma concentration occurs 0.5 to 4 hours after oral dosing, with an elimination half-life of approximately 13 hours. Pharmacokinetics are proportional to oral dose over the range of 100 to 800mg. Both 60- and 30-minute infusions of LCM are bioequivalent to oral LCM in healthy subjects. Trial SP616 was a double-blind, double-dummy investigation of the pharmacokinetics (PK) and safety of intravenous (iv) LCM (10mg/mL) as replacement of adjunctive oral LCM in adults with partial-onset seizures. Subjects (n=60) receiving adjunctive, stable, twice daily doses (200 to 600mg/day) of oral LCM tablets in an open-label extension trial were randomized 2:1 to receive the same dose as iv LCM plus placebo (PBO) tablets bid or iv PBO plus oral LCM bid, respectively, for 2 consecutive days. Subjects (n=30) in Cohort A received 60-minute infusions. Next, subjects (n=30) in Cohort B received 30-minute infusions. Serial ECGs and vital signs data were collected. PK sampling was performed for the morning dose on Day 2 ( predose, Hours 0.5, 1, 1.5, 2, 4, 8, and 12 after start of dose). PK parameters were analyzed based on descriptive statistics and between-group ratios. Fifty-nine subjects completed. No clear differences in AE reports, ECG intervals, blood pressure, or heart rate were observed between the iv LCM and oral LCM groups.
Administration of LCM as 60- and 30-minute infusions resulted in similar plasma concentration time curves and PK parameters compared to oral administration after normalizing for body weight and dose.[table1] The t[sub]max[/sub] most commonly occurred at the end of LCM infusion (eg, 30 min for Group B) and later for oral dosing (eg, 1.5 to 4 hr for 54% of subjects in Group B). In this trial, the safety profile after 60- and 30-minute infusions of lacosamide was comparable to that observed after oral dosing. In addition, 60- and 30-minute infusions of lacosamide resulted in comparable pharmacokinetics and bioavailability to that after oral dosing. (Supported by Schwarz Biosciences, Inc.)