Abstracts

Rationale: AED plasma concentrations are occasionally measured as routine medication management, even for drugs with no recognized therapeutic range. Comparison of serum concentrations to an established baseline for an individual patient can be a useful tool to identify reasons for unexpected changes in drug effectiveness or tolerability. In this respect, it is helpful to know typical concentrations expected for various doses of a new AED. Lacosamide (Vimpat®) was recently approved for adjunctive treatment of partial-onset seizures in adults. An intravenous (IV) formulation of lacosamide is also available for use when oral therapy is not feasible. The safety of IV lacosamide, given over infusion durations of 30, 15, or 10 minutes, was studied as a short-term replacement (3-5 days) for oral lacosamide in 160 patients receiving lacosamide as part of a long-term, open-label extension trial. An analysis of pharmacokinetic data from this trial, including peak and trough concentrations for different lacosamide doses, is reported here. Methods: Serial cohorts of subjects were converted from oral treatment to the same IV lacosamide dose, using progressively shorter infusion durations for each cohort. Blood samples for the assessment of lacosamide plasma concentrations were obtained prior to the last oral dose on Study Day -1, prior to and following IV infusions on Study Days 1 and 2, and prior to resuming oral dosing at the end of the trial (Days 3-6). Descriptive statistics for lacosamide plasma concentrations (C_{trough oral}, C_{trough iv}, C_{max iv}) are calculated by dose. Results: Of 1593 plasma samples obtained in the trial, a total of 1364 LCM plasma concentrations, comprising data from 149 subjects (n= 20, 93 and 36 for the 30-,15-, and 10-minute infusion duration cohorts, respectively), were considered valid for analysis. The figure depicted below shows the average lacosamide plasma concentrations by timepoint (day -1 through End of IV Treatment Period [EOTP]) and dose for the 15-minute infusion duration cohorts. Overall, the average lacosamide C_max and C_trough plasma concentrations appeared dose proportional under oral and IV doses within the dose range of 200-800mg/day (100-400mg bid). Both parameters were similar for consecutive dosing days. C_trough appeared similar for oral and IV doses. Similar results were seen for the 10-minute and 30-minute infusion duration groups. Conclusions: Lacosamide peak and trough plasma concentrations appeared dose-proportional and stable across consecutive dosing days at steady state. Substitution of IV for oral lacosamide resulted in similar plasma concentrations and drug exposure.