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To explore the influencing factors of lacosamide serum concentration in children with epilepsy, and to provide evidence-based guidance for individualized dosing strategies. Clinical data of pediatric epilepsy patients treated with lacosamide from September 2021 to January 2025 were retrospectively analyzed. Participants were stratified by age into ≤6, 6-12, and >12 years groups. Non-parametric tests were employed to compare differences in daily dose, weight-adjusted daily dose, serum concentration, and concentration-to-dose ratio (CDR) across sex, age, and concomitant antiepileptic drugs (AEDs) groups. Multiple linear regression analysis was conducted to identify independent factors influencing serum concentration. The study enrolled 438 patients (boys: 261, 59.59%; girls: 177, 40.41%), with age distribution as follows: ≤ 6 years (n = 85, 19.41%), 6-12 years (n = 294, 67.12%), and >12 years (n = 59, 13.47%). The > 12 years group exhibited significantly higher daily dose, weight-adjusted daily dose, and CDR compared to younger cohorts. Concomitant use of non-hepatic enzyme-inducing AEDs resulted in elevated serum concentration and CDR relative to lacosamide monotherapy. Regression analysis identified body weight, weight-adjusted daily dose, and coadministration of non-hepatic enzyme-inducing AEDs as independent predictors of serum concentration. Age and concomitant non-hepatic enzyme-inducing AEDs therapies significantly influence lacosamide exposure, underscoring the necessity for age-based dynamic dose optimization and rigorous evaluation of polypharmacy regimens to achieve precision therapeutics.

Saliva, known for better patient compliance and simpler collection, is ideal for monitoring antiseizure medication (ASM) levels. This study aimed to validate saliva for measuring lacosamide, develop a pharmacokinetic (PK) model, and determine the optimal saliva concentration for seizure control in epilepsy patients. In our prospective study at Seoul National University Hospital from August 2021 to November 2022, we enrolled lacosamide-prescribed epilepsy patients, collecting their saliva and blood samples. We developed a population PK model with nonlinear mixed-effects modeling, incorporating a saliva compartment and plasma-to-saliva distribution scaling factor. The model, factoring in CYP2C19 genotypes, demographics, and concurrent ASM use, estimated optimal saliva lacosamide concentration cutoffs for well-controlled seizures in high seizure burden patients. These values were validated through a two-year longitudinal analysis. In our study, 123 epilepsy patients prescribed lacosamide were finally analyzed. We identified 74 matched pairs of blood and saliva samples, finding a linear relationship between their lacosamide concentrations (R = 0.62, P  < 0.001). Using our PK model, we estimated individual peak (C max ) and trough concentrations in saliva and blood based on dosage, determining optimal saliva cutoffs for well-controlled seizure status in lacosamide: 15.94 mg/L for C max and 9.056 mg/L for trough, with 72.7% sensitivity and 88.2% specificity. Longitudinal analysis showed well-controlled seizure status achievement aligning with times when estimated C max and trough surpassed these cutoffs. Our research presents the potential and validity of using saliva concentration as an alternative to blood concentration for lacosamide TDM, advancing personalized pharmacotherapy in epilepsy treatment.

Lacosamide is a third-generation antiepileptic drug used for the treatment of partial-onset seizures. This study investigates the development and validation of a novel analytical method for the determination of lacosamide in human plasma and pharmaceutical formulations using boron and nitrogen co-doped graphene quantum dots (BN-GQDs). The prepared BN-GQDs exhibited excellent fluorescence properties that quenches in the presence of lacosamide, allowing for its sensitive detection. Density functional theory calculations and Stern-Volmer analysis were used to elucidate the mechanism of this fluorescence quenching, which was influenced by various factors optimized using a central composite design. The proposed method was validated according to ICH M10 guidelines displaying excellent linearity in the range of 0.1–5 µg/mL, with a limit of detection of 0.033 µg/mL. Accuracy, precision, selectivity and robustness were also evaluated, and the results met the acceptance criteria of the guidelines. Hence, the method was successfully applied to quantify lacosamide in pharmaceutical formulations and pharmacokinetic studies, demonstrating its capabilities in bioanalytical applications. Assessment of the environmental impact and sustainability of the proposed method showed significant improvement, particularly in whiteness and overall performance posing its advantages for routine quality control analysis and therapeutic drug monitoring of lacosamide.

There is still a need for new antiepileptic drugs (AEDs) as the clinical efficacy, tolerability, toxicity or pharmacokinetic properties of existing AEDs may not be satisfactory. One new AED has recently been approved (rufinamide in 2007) and six others are in late-stage development (phase III and onwards) [brivaracetam, carisbamate, eslicarbazepine, lacosamide, retigabine and stiripentol]. The purpose of this review is to provide updated data on proposed mechanisms of action, efficacy and tolerability on these new AEDs, and to discuss the rationale for their development and possible advantages compared with existing treatment, based on recent publications and MEDLINE searches. Rufinamide, brivaracetam and stiripentol have been given the status of orphan drugs. Rufinamide was approved in Europe in 2007 for the use in Lennox-Gastaut syndrome. Brivaracetam has gained orphan status for development in progressive and symptomatic myoclonic seizures in Europe and the US, respectively. Stiripentol has gained orphan status in children with Dravet’s syndrome and pharmaco-resistant epilepsy. All of these drugs demonstrate efficacy as adjunctive therapy in partial seizures. Three of the drugs are derivatives of existing AEDs: brivaracetam is a derivative of levetiracetam with improved affinity for the target molecule; carisbamate is a derivative of felbamate with improved tolerability; and eslicarbazepine is a derivative of carbamazepine with less interaction potential and no auto-induction. Lacosamide, retigabine, rufinamide and stiripentol are new compounds, unrelated to other AEDs. Further investigation and development of new broad-spectrum drugs is important for improved treatment of patients with epilepsy and other neurological and psychiatric disorders.

ObjectiveTo evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic generalised epilepsy (IGE).MethodsPhase 3, double-blind, randomised, placebo-controlled trial (SP0982; NCT02408523) in patients with IGE and PGTCS taking 1–3 concomitant antiepileptic drugs. Primary outcome was time to second PGTCS during 24-week treatment.Results242 patients were randomised and received ≥1 dose of trial medication (lacosamide/placebo: n=121/n=121). Patients (mean age: 27.7 years; 58.7% female) had a history of generalised-onset seizures (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). Median treatment duration with lacosamide/placebo was 143/65 days. Risk of developing a second PGTCS during 24-week treatment was significantly lower with lacosamide than placebo (Kaplan-Meier survival estimates 55.27%/33.37%; HR 0.540, 95% CI 0.377 to 0.774; p<0.001; n=118/n=121). Median time to second PGTCS could not be estimated for lacosamide (>50% of patients did not experience a second PGTCS) and was 77.0 days for placebo. Kaplan-Meier estimated freedom from PGTCS at end of the 24-week treatment period (day 166) for lacosamide/placebo was 31.3%/17.2% (difference 14.1%; p=0.011). More patients on lacosamide than placebo had ≥50% (68.1%/46.3%) or ≥75% (57.1%/36.4%) reduction from baseline in PGTCS frequency/28 days, or observed freedom from PGTCS during treatment (27.5%/13.2%) (n=119/n=121). 96/121 (79.3%) patients on lacosamide had treatment-emergent adverse events (placebo 79/121 (65.3%)), most commonly dizziness (23.1%), somnolence (16.5%), headache (14.0%). No patients died during the trial.ConclusionsLacosamide was efficacious and generally safe as adjunctive treatment for uncontrolled PGTCS in patients with IGE.

To evaluate the effects of cytochrome P450 family 2 subfamily C member 9 ( CYP2C9 ) and cytochrome P450 family 2 subfamily C member 19 ( CYP2C19 ) polymorphisms on the plasma concentrations, efficacy, and safety of lacosamide (LCM) among pediatric patients with epilepsy. This prospective study was conducted at two institutions. It included 215 pediatric patients with epilepsy who were under LCM. LCM plasma concentrations were quantified using validated ultra-performance liquid chromatography. CYP2C9 and CYP2C19 polymorphisms were analyzed in all pediatric patients in our hospital's Institute of Clinical Pharmacy research laboratory through polymerase chain reaction, agarose gel electrophoresis detection, gel recovery, and other steps. Seizure frequencies were recorded 3, 6, and 12 months after initiating LCM therapy and compared with the baseline monthly frequency. Clinical information, including efficacy, toxicity, and concomitant drugs, was collected. A total of 158 pediatric patients (73.5%) responded to LCM therapy. Of them, 77 patients reported adverse events while under LCM. The LCM plasma concentration was linearly correlated with its daily dose ( r  = 0.26, p  < 0.001). Patients with adverse events reported higher LCM plasma concentrations (7.9 ± 4.0 µg/mL) than patients without adverse events (6.8 ± 3.0 µg/mL; p  < 0.05). The poor metabolizer (PM) group demonstrated the highest concentration-to-dose ratio (1.7 ± 0.7 μg·mL −1 ·kg·mg −1 ) than the extensive metabolizer, intermediate metabolizer, and ultra-rapid metabolizer groups (0.8 ± 0.4, 1.0 ± 0.5, and 0.8 ± 0.4 μg·mL −1 ·kg·mg −1 , respectively). The PM group comprised the highest proportion of patients with effective LCM (9/11, 81.8%) and adverse events (7/11, 63.6%). Conclusion : LCM plasma concentrations were strongly associated with its clinical efficacy and toxicity. CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in pediatric patients with epilepsy. CYP2C19 PMs with two no-function alleles are likely to have higher LCM plasma concentrations. What is Known: • LCM is metabolized by CYP2C19, CYP2C9, and CYP3A4 into pharmacologically inactive O-desmethyl-lacosamide; it primarily undergoes renal elimination. • Plasma LCM concentrations in patients treated with the recommended dose vary widely between and within individuals variability. What is New: • CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in Chinese pediatric patients with epilepsy. • CYP2C19 PMs with two no-function alleles are likely to have higher plasma LCM concentrations.

Aims To evaluate the efficacy, safety, and tolerability of adjunctive lacosamide therapy against focal seizures in young children (1 month – 4 years). Methods This non‐randomized, open‐label, and self‐controlled real‐world study included 105 children (1 month–4 years) with focal seizures treated with adjunctive lacosamide therapy at Children's Hospital of Chongqing Medical University. Results (1) The 50% response rates at 3, 6, 9, and 12 months of follow‐up were 58.1%, 61.0%, 57.1%, and 56.2%, while the seizure‐free rates were 27.6%, 34.3%, 32.4%, and 37.1%, respectively. The 50% response rate of the first addition of lacosamide for focal seizures was much higher than the second and later added treatment at 3 months (p = 0.038). After 1 year of follow‐up, these children showed an improvement in neurodevelopmental levels (p < 0.05). (2) Lacosamide retention rate was 72.7% (64/88) after 1 year of follow‐up. Lack of efficacy and serious adverse events were independent risk factors for the lacosamide retention rate. (3) During adjunctive lacosamide therapy, 13 (12.4%) patients reported adverse events and five (4.7%) patients withdrew due to adverse events, including vomiting drowsiness, ataxia (0.94%), neck itching with eczema (0.94%), irritability (1.88%), and gastrointestinal discomfort (0.94%). Conclusion Adjunctive lacosamide therapy was effective, safe, and well‐tolerated in young Chinese children with focal seizures in this study. Lacosamide (LCM) is effective, safe, and well‐tolerated as an adjunctive therapy in young Chinese children aged ≥1 month to ≤4 years. The order of lacosamide introduction significantly influenced its short‐term efficacy.

Purpose Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. Methods In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. Results We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26–51%) versus 30% (95%CI 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. Conclusion Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

Background Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response. Methods This study will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel, phase 2, proof-of-concept, phenotype-stratified study. The study will enroll 108 patients with peripheral neuropathic pain who will be randomized to a 12-week treatment with lacosamide or placebo up to 400 mg/day in a 2:1 ratio. The primary objective is to compare the change in the mean value of the patients’ daily ratings of average pain intensity from baseline to the last week of treatment in patients with and without the irritable nociceptor phenotype in the per-protocol population. A supportive objective is to compare the effect of lacosamide with that of placebo in the two phenotypes. Secondary and tertiary outcomes include the Patient Global Impression of Change, pain relief, presence of 30% and 50% pain reduction, sleep disturbance, depression, and anxiety. Discussion We will examine the concept of individualized therapy based on phenotyping, and expect that this study will provide important information on the usefulness of lacosamide in the treatment of peripheral neuropathic pain. Trial registration ClinicalTrials.gov, NCT03777956 . Registered on 18 December 2018.

IntroductionEpilepsy ranks as one of the most prevalent neurological disorders, with poorly controlled seizures imposing a significant disease burden. Subclinical epileptiform discharges (SEDs) have been linked to cognitive and behavioural impairments in children. There is a growing trend in clinical practices towards increased use of antiseizure medications (ASMs), as they have the potential to alleviate the impact of SEDs in children. Nonetheless, 25–30% of epilepsy patients do not respond to current antiepileptic treatments. Lacosamide (LCM), a third-generation ASM, has demonstrated established efficacy and tolerability in both adults and children with epilepsy. However, there is a scarcity of studies on LCM as a monotherapy for paediatric patients with epilepsy and SEDs. This study aims to assess the efficacy and safety of LCM monotherapy in epilepsy patients, as well as to examine the impact of LCM on patients with SED.MethodsThis prospective cohort study, conducted at a single centre and employing an open-label approach, aims to administer LCM antiepileptic treatment to children while taking into account their seizure profiles, electroencephalogram results, cognitive development and other relevant factors. The index date, marking the administration of the first LCM dose, defines the beginning of the study. The baseline period encompasses the 3 months leading up to the index date, and each child will be monitored until the addition, switch or discontinuation of study drugs, death, completion of a full 1-year follow-up or the conclusion of the study period. Assessments will be conducted every 3 months throughout the follow-up period.Ethics and disseminationThis study received approval from the Ethics Committee of the Children’s Hospital Affiliated with Chongqing Medical University (file number: 2024-210), and all participating sites have obtained the necessary approvals. This study has been registered with the Chinese Clinical Trial Registry. Written informed consent will be sought from the parents or guardians of potential participants under 16 years of age at the outpatient clinic. Additionally, older children with normal cognitive function will be asked to provide their own version of written informed consent. Participation in the study is voluntary, and individuals or their parents/guardians who choose not to provide consent will not be included in the study.Trial registration numberChiCTR2400092710.