Absorption, disposition, metabolic fate and elimination of the anti-epileptic drug lacosamide in humans: mass balance following intravenous and oral administration

Abstract

The absorption, distribution, metabolism and elimination of the anti-epileptic drug lacosamide were determined in 10 healthy male volunteers following intravenous or oral administration in a single-center, open-label, single-dose trial. Volunteers were randomized to receive either a continuous intravenous infusion of 100 mg (40 μCi) [¹⁴C]-lacosamide administered over 60 min, or a 100 mg (40 μCi) [¹⁴C]-lacosamide dose given as an oral solution. During the infusion, total radioactivity concentrations reached peak levels at 1 h post dose followed by a decline of 71 % within 24 h. More than 97 % of radioactivity was excreted within 168 h; 96.8 % in urine and 0.3 % in feces. Following oral administration, total radioactivity concentrations increased to peak levels within 0.5 h followed by a decline of 65 % within 24 h. Approximately 94.6 % of radioactivity was excreted within 168 h after oral administration, 94.2 % by the kidneys and 0.4% in feces. A comparison of AUC values (po/iv) of unchanged lacosamide indicates a high absolute bioavailability. The metabolic profile was analyzed using pooled urine samples, and following intravenous and oral administration, respectively, a total of 38 and 34 % unchanged lacosamide, 28 and 28 % of the desmethyl metabolite and 19 and 17 % of a polar fraction were measured. Additional metabolites were identified only in small amounts (<3 %). In plasma at maximum concentration, most of the total radioactivity was found as unchanged drug after intravenous and oral dose. The plasma concentration curves of total radioactivity following intravenous and oral administration were similar.