An Analytical Study to Correlate Serum Levels of Levetiracetam with Clinical Course in Patients with Epilepsy

Abstract

Introduction:With the advancement of therapeutics, newer antiepileptic drugs (AEDs) like Levetiracetam (LEV), with good therapeutic efficacy and tolerability are available. But unfortunately, therapeutic drug monitoring is not routinely done in India for these drugs.Objectives:The objective of this study is to determine the range of serum levels of LEV in patients at stabilized doses and correlate them with their clinical course.Materials and Methods:Patients with epilepsy and started on LEV were enrolled from the Neurology Department after the Ethics Committee approval. Serum levels of LEV were estimated using high-performance liquid chromatography and correlated with patient demographics, dosage, dosage forms, concomitant AEDs, compliance of the patient, therapeutic effect, adverse drug reactions (ADRs), and suspected toxicity.Results:Serum levels of LEV ranged from 0.4 to 102.2 μg/ml at different time points and demonstrated a negligible positive correlation with age of the patients (r = 0.12) but negligible negative correlation with bodyweight (r = −0.19). No conclusive relationship could be established for dose, gender, dosage forms, clinical efficacy (seizure frequency), ADRs, and toxicity. Compliance was verified in all the patients. Levels were found to reduce with the use of concomitant enzyme inducer drugs (56.78%) whereas increase with valproic acid (7.8%).Conclusion:These findings emphasize the need for monitoring the serum levels of newer AEDs like LEV considering the various parameters studied here, so as to maintain the therapeutic efficacy by preventing under or over dosage and to generate a broader database of serum levels of LEV in the Indian population to help appropriate prescribing with more confidence.

Correlation of levetiracetam concentration in peripheral blood mononuclear cells with clinical efficacy: A sensitive monitoring biomarker in patients with epilepsy

“…Contrarily, LEV C u.serum did not express a significant correlation with patients' clinical response. This was generally comparable to most clinical studies that correlated LEV serum level to its clinical efficacy [16,[27][28][29]. This is because AEDs clinical efficacy is generally tied to their concentrations at target brain sites, which is not seemingly represented by LEV serum concentration.…”

“…Consequently, Sheinberg et al [28] concluded that the benefit of LEV serum TDM may be only limited to individuals with potential lack of compliance, for therapeutic baseline detection after satisfactory response, or in severe toxicity. Likewise, in epilepsy patients with wide range of age and add-on AEDs, Lancelin et al [16] and Gupta et al [29] showed a non-conclusive relationship between LEV serum concentration and its clinical efficacy.…”

Clinical Pharmacology in India-A Systematic Review of Research in the Past 5 Years

“…The latter finding had been seen previously in a study in which among patients clinically suspected of having phenytoin toxicity, only 59% had plasma concentrations above the reference levels (Taur et al, 2013). Another study emphasized the need for monitoring the serum levels of even newer antiepileptics like levetiracetam as its levels decreased by about 57% when enzyme inducers were used concomitantly (Gupta et al, 2016).…”

Review on the relevance of therapeutic drug monitoring of levetiracetam

“…Third, the outcome measure differed between studies, making a direct comparison difficult. Fourth, three of the included studies [9,17,34] did not report the timing of the blood draw. LEV SDC should be the trough concentration (immediately before the next dose) since large fluctuations in LEV SDCs are possible due to its short half-life (6-8 h) [1].…”