Ex Vivo Assessment of Lamotrigine Clearance During Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) provides renal support for unstable ICU patients but significantly alters drug concentrations. For patients on long-term antiepileptics such as lamotrigine, CRRT may increase risk for breakthrough seizures due to subtherapeutic levels. Conversely, CRRT may aid in lamotrigine overdose. While partial clearance of lamotrigine by intermittent hemodialysis has been reported, CRRT clearance is not well studied. This study determined lamotrigine extraction by CRRT in an ex vivo system. Medication was administered at two concentrations: one therapeutic and one supratherapeutic to closed-loop, blood-primed, ex vivo CRRT circuits. Drug concentrations were measured in plasma, hemofiltrate (effluent), and matching control samples at specific time points. For each time point, percent recovery of lamotrigine was calculated, and differences between CRRT circuits and controls were analyzed using two-sample t-tests. Plasma lamotrigine concentrations decreased rapidly, with 10% (n = 3, SD = 4%) and 17% (n = 2, SD = 3%) recovery at four hours for therapeutic and supratherapeutic doses, respectively. Although lower starting concentrations trended toward greater clearance, differences were not statistically significant ( P = .13). Control concentrations remained stable, with approximately 100% recovery. Lamotrigine concentrations were significantly affected by CRRT circuits. Patients receiving lamotrigine who require CRRT may need dosing adjustments to maintain clinical efficacy. Additionally, CRRT effectively clears lamotrigine, suggesting potential utility in overdose management.