This in vitro investigation assessed how the antiepileptic drug lacosamide interacts with common hemodialysis and continuous renal replacement therapy (CRRT) filter membranes. The study aimed to determine whether lacosamide adsorbs to different membrane materials and whether the drug remains chemically stable in saline and plasma matrices during short-term extracorporeal circulation. Findings are relevant to critically ill renal patients receiving lacosamide during extracorporeal therapies.
Lacosamide was prepared at a concentration of 200 µg/mL in two matrices: 0.9% sodium chloride (saline) and bovine plasma. These solutions were perfused through three distinct dialysis filters representative of membranes used in extracorporeal therapies: polysulfone (PS), polyacrylonitrile (PAN), and polyacrylonitrile polyethyleneimine (PAN-PEI). The study evaluated adsorption by measuring lacosamide concentrations at serial timepoints after starting perfusion.
Samples were collected at 0, 5, 15, 30, 45, 60, and 90 minutes during perfusion. Lacosamide concentrations in collected samples were quantified using high-performance liquid chromatography (HPLC). Changes in concentration over time and differences among filter types were assessed using repeated-measures analysis of variance with post hoc tests as appropriate.
The study reported that lacosamide demonstrated chemical stability in both 0.9% NaCl and bovine plasma over the 90-minute observation period. Concentration variation in these solutions was under 7% across the 90 minutes, indicating that observed reductions in perfusate concentration during filter testing are unlikely to be caused by spontaneous degradation in the tested matrices.
When lacosamide in saline was passed through the filters, measurable adsorption to all three membrane types occurred over 90 minutes. Reported total concentration reductions at 90 minutes in saline were:
These results indicate that, in the saline model, the PS membrane showed the largest proportionate decrease in perfusate lacosamide concentration over the 90-minute interval.
In the bovine plasma model, lacosamide adsorption patterns differed from saline. Total reductions at 90 minutes in plasma were reported as:
For the PAN and PAN-PEI membranes, adsorption was greater in plasma than in saline, whereas the PS membrane demonstrated greater adsorption in saline than in plasma.
Although measurable adsorption occurred with all membranes and in both matrices, the authors report that no statistically significant differences in adsorption were detected among the three filter types (P > 0.05). Thus, while numerical differences were observed in percentage reductions, these did not reach statistical significance within the parameters of the experiment.
The study concludes that lacosamide is chemically stable but subject to measurable adsorption to artificial membranes used in extracorporeal circulation. Because adsorption led to decreased lacosamide concentration in the perfusate, there is potential for reduced circulating drug levels during hemodialysis or CRRT. Clinicians should be aware that extracorporeal circuits may lower lacosamide exposure in critically ill renal patients, and this factor should be considered when planning dosing during or around extracorporeal therapies.
Key methodological points to consider:
These limitations mean that while the findings signal a potential for clinically relevant drug loss, direct clinical dosing recommendations or changes in practice are not provided in the source article.
The in vitro data indicate that lacosamide remains stable in saline and plasma for at least 90 minutes but exhibits adsorption to dialysis membranes commonly used in CRRT. Adsorption patterns varied by membrane and matrix, with numerically greater losses for PS in saline and for PAN/PAN-PEI in plasma; however, differences among membranes were not statistically significant. Clinicians should consider the possibility of reduced lacosamide concentrations during extracorporeal circulation in critically ill renal patients and account for this when managing antiepileptic therapy during hemodialysis or CRRT. The source does not present clinical outcome data or prescriptive dosing adjustments.