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.
Highlights
Levetiracetam (LEV) is a second-generation antiepileptic drug (AED) approved for use in the treatment of refractory partial seizures with or without secondary generalized seizures in an oral formulation and for intravenous use [1].LEV is absorbed rapidly, reaching peak concentrations within 1 h after intake with almost complete oral bioavailability [2]
We investigated the current status of LEV therapeutic drug monitoring (TDM) as well as the influence of other AEDs in Korean patients with epilepsy
Even though our data showed a relatively wide dose and concentration range with a high poly-AED therapy ratio, the proportion within the therapeutic range was comparable to other studies, implying the importance of LEV TDM in our center’s clinical settings (Table 4)
Summary
LEV is absorbed rapidly, reaching peak concentrations within 1 h after intake with almost complete oral bioavailability [2]. Half-life of LEV is 6–8 h in healthy adults, reaching steady states within 48 h [4,5,6,7]. Metabolism of LEV is not dependent on the hepatic cytochrome P450 system, whereas the acetamide group of plasma hydroxylase is involved [2,6]. LEV has a low side-effect rate, a wide daily dose range (250–5000 mg), and favorable patient compliance [3,4], being a valuable treatment option for acute seizure, critically ill patients [8,9,10], and patients in the outpatient department
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