Therapeutic Drug Monitoring of Levetiracetam by High-Performance Liquid Chromatography With Photodiode Array Ultraviolet Detection: Preliminary Observations on Correlation Between Plasma Concentration and Clinical Response in Patients With Refractory Epilepsy

Abstract

Levetiracetam is a new antiepileptic drug prescribed for the treatment of patients with refractory partial seizures with or without secondary generalization as well as for the treatment of juvenile myoclonic epilepsy. A rapid and specific method by high-performance liquid chromatography diode array detection was developed to measure the concentration of levetiracetam in human plasma. The trough plasma concentrations measured in 69 epileptic patients treated with 500 to 3000 mg/d of levetiracetam ranged from 1.1 to 33.5 microg/mL. The mean (range) levetiracetam plasma concentrations in responders and nonresponders were 12.9 microg/mL (4.6-21 microg/mL) and 9.5 microg/mL (1.1-20.9 microg/mL), respectively. A wide variability in concentration-response relationships was observed in patients. Using a receiver operating characteristic curve, the threshold levetiracetam concentration for a therapeutic response was 11 microg/mL. The sensitivity and specificity for this threshold levetiracetam concentration were 73% and 71%, respectively. According to chi analysis, this finding was not significant probably because of the small number of patients and because of their refractory seizure type. Nevertheless, the levetiracetam plasma concentration could be used to help clinicians detect severe intoxication or to verify compliance by repeating the measurement in patients.

Simple and validated HPLC–UV analysis of levetiracetam in deproteinized plasma of patients with epilepsy

“…pregnancy), in pathological states such as renal impairment and in specific age groups (children and the elderly) [2,3]. Different HPLC methods for the determination of LEV in human plasma have been reported, coupled with UV [4][5][6][7] or diode array detection [8,9], mostly after sample pretreatment by expensive solid-phase extraction [4] or time-consuming liquid-liquid extraction procedures [5,7,9]. The availability of simple, accurate and inexpensive analytical assays is crucial for the successful use of TDM in clinical practice.…”

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

“…Numerous chromatographic methods have been reported for the quantification of LVT in biological fluids. Different HPLC methods for the determination of LVT in human plasma have been reported coupled with UV [182,183] or diode array detection [23,184,185], mostly after sample pretreatment by expensive solid-phase extraction or time-consuming liquid-liquid extraction procedures [183,185]. The availability of simple, accurate and inexpensive analytical assays is crucial for the successful use of TDM in clinical practice.…”

Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

“…Several chromatographic methods have been published for quantification of LEV concentrations in biological fluids such as saliva and plasma (or serum) for TDM and in urine for pharmacokinetic aims. They include different subtypes of liquid chromatography with various detection systems (Contin et al, 2008;Grim et al, 2003;Guo et al, 2007;Jain et al, 2006;Juenke et al, 2006;Kuhn, Knabbe, 2013;Lancelin et al, 2007;Martens-Lobenhoffer, BodeBoger, 2005;Matar, 2008;Pucci et al, 2004;Rao et al, 2004;Ratnaraj, Doheny, Patsalos, 1996;Shibata et al, 2012), gas chromatography (Isoherranen et al, 2000;Mecarelli et al, 2007) and microemulsion electrokinetic chromatography (Ivanova et al, 2003). An analytical nonchromatographic method, capillary electrophoresis, is also described (Shihabi, Oles, Hinsdale, 2003).…”