title: 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.
authors: Departments of Biology, Centre Hospitalier Sainte-Anne, Paris, France. l.lancelin@ch-sainte-anne.fr
authors: Frédérique
authors: F
authors: Lancelin
authors: Emilie
authors: E
authors: Franchon
authors: Linda
authors: L
authors: Kraoul
authors: Isabelle
authors: I
authors: Garciau
authors: Sophie
authors: S
authors: Brovedani
authors: Khalid
authors: K
authors: Tabaouti
authors: Elisabeth
authors: E
authors: Landré
authors: Francine
authors: F
authors: Chassoux
authors: Pascal
authors: P
authors: Paubel
authors: Marie-Liesse
authors: ML
authors: Piketty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods; D004351:Drug Resistance; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam