Levetiracetam Therapeutic Drug Monitoring in a Large Cohort of Korean Epileptic Patients

Abstract

Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography–tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20–5000) mg and 25.5 (3.03–133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8–95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients.

Ag Nanoislands Modified Carbon Fiber Nanostructure: A Versatile and Ultrasensitive Surface-Enhanced Raman Scattering Platform for Antiepileptic Drug Detection

“…In addition, the Ag nanoislands with different morphologies generated multi-level electromagnetic enhancement "hot spots", Levetiracetam, another drug used in adults and children over 4 years of age with epilepsy, was successfully detected by using Raman scattering spectroscopy. As an antiepileptic drug, excessive dosage of levetiracetam may cause drowsiness, agitation, aggression, decreased level of consciousness, respiratory depression and coma and other clinical adverse reactions [49]. The results of levetiracetam Ames test, Chinese hamster ovary cells/hypoxanthine-guanine phosphoribosyl transferase locus mammalian cell gene mutation test, Chinese hamster ovary cell chromosome aberration test and mouse micronucleus test were all negative.…”

Pharmacokinetics in Pharmacometabolomics: Towards Personalized Medication

“…A frequently employed approach for personalized drug administration in clinical settings, TDM, predominantly concentrates on the surveillance of drug metabolism (pharmacokinetics). However, it omits consideration of inter-individual metabolic variations among patients and thus falls short in its capacity to prognosticate drug response during the drug delivery process [142]. Pharmacometabolomics is the most promising method for personalized medication.…”

Design and Production of DNA-Based Electrochemical and Biological Biosensors for the Detection and Measurement of Gabapentin Medication in Clinical Specimens

“…5 Measurement of antiepileptic drugs in serum or plasma is now considered a proper function in epilepsy treatment. 6 The purpose of TDM in antiepileptic drugs is to optimize the therapeutic output of patients through drug regimen management and drug concentration/level measurement. 7 Gabapentin was produced in the USA in 1994 to treat epilepsy and then used to treat chronic pains.…”