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Levetiracetam therapeutic drug monitoring

Shery Jacob, Anroop B Nair
Given the distinctive characteristics of both epilepsy and antiepileptic drugs (AEDs), therapeutic drug monitoring (TDM) can make a significant contribution to the field of epilepsy. The measurement and interpretation of serum drug concentrations can be of benefit in the treatment of uncontrollable seizures and in cases of clinical toxicity; it can aid in the individualization of therapy and in adjusting for variable or nonlinear pharmacokinetics; and can be useful in special populations such as pregnancy. This review examines the potential for TDM of newer AEDs such as eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, perampanel, pregabalin, rufinamide, retigabine, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide...
October 20, 2016: Drugs in R&D
Fawzia A Ibrahim, Amira F El-Yazbi, Magda A Barary, Mira M Wagih
AIM: Recently, polytherapy regimen has been introduced for the treatment of epileptic patients for better seizure control with lesser side effects and better control of multiple seizure types. METHODOLOGY: A simple, sensitive and highly specific reversed-phase HPLC method was developed for simultaneous determination of four antiepileptic drugs (AEDs), levetiracetam, lamotrigine, oxcarbazepine and carbamazepine, in real human plasma without interference from endogenous components of plasma...
November 2016: Bioanalysis
Yuichi Kubota, Hidetoshi Nakamoto, Takakazu Kawamata
Herein, we review the current state of nonconvulsive status epilepticus (NCSE). NCSE has recently been recognized as one of the causes of unexplained impaired consciousness in the neurosurgical or neurocritical setting. The causes of NCSE include not only central nervous system disorders such as craniotomy, stroke, traumatic brain injury, and central nervous system inflammation, but also severe critical conditions such as sepsis and uremia, among others. NCSE shows no overt clinical manifestations; therefore, prompt and correct diagnosis is difficult...
October 15, 2016: Neurologia Medico-chirurgica
Julien Dupouey, Natalia Doudka, Séphora Belo, Olivier Blin, Romain Guilhaumou
Therapeutic drug monitoring of antiepileptic drugs is widely practiced to achieve optimal efficacy and avoid adverse side effects. We describe an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC/MS/MS) method developed for the monitoring of 4 frequently prescribed antiepileptic drugs including lamotrigine, levetiracetam, oxcarbazepine and topiramate. Main pharmacologically active metabolite of oxcarbazepine (mono-hydroxy-derivative metabolite, MHD) was also quantified. After addition of internal standards and a simple stage of protein precipitation, plasmatic samples were analyzed on a C18 column...
July 15, 2016: Biomedical Chromatography: BMC
Manuela Contin, Lucia Alberghini, Carmina Candela, Giulia Benini, Roberto Riva
Generic substitution of antiepileptic drugs (AEDs) is still a matter of controversy and concern among clinicians and patients. We aimed to assess intrasubject variation in plasma concentrations of lamotrigine (LTG), levetiracetam (LEV) and topiramate (TPM) after generic substitution compared with a stable brand-name drug regimen in a population of patients with epilepsy. A retrospective analysis was performed on prospectively collected and stored data from our therapeutic drug monitoring (TDM) database for the years 2009-2014...
May 2016: Epilepsy Research
Satoko Ito, Ikuko Yano, Sachiyo Hashi, Masahiro Tsuda, Mitsuhiro Sugimoto, Atsushi Yonezawa, Akio Ikeda, Kazuo Matsubara
BACKGROUND: Levetiracetam, a second-generation antiepileptic drug, is frequently used for managing partial-onset seizures. About 70% of the administered dose is excreted in urine unchanged, and dosage adjustment is recommended based on the individual's renal function. In this study, a population pharmacokinetic model of levetiracetam was developed using routinely monitored serum concentration data for individualized levetiracetam therapy. METHODS: Patients whose serum concentrations of levetiracetam at steady-state were routinely monitored at Kyoto University Hospital from April 2012 to March 2013 were enrolled...
June 2016: Therapeutic Drug Monitoring
Lei Yin, Tingting Wang, Meiyun Shi, Ying Zhang, Xiaojun Zhao, Yan Yang, Jingkai Gu
A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample...
March 2016: Journal of Separation Science
Ah-Reum Ko, Tae-Cheon Kang
PURPOSE: To elucidate the mechanisms that regulate p-glycoprotein (PGP) expression and function in pharmacoresistant epilepsy, we investigated the effect of an ETB receptor antagonist (BQ788) and a p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190) on intractable seizures in chronic epileptic rats. METHODS: Lithium-pilocarpine-induced chronic epileptic rats were used in the present study. Animals were given levetiracetam (LEV), LEV + SB202190, LEV + BQ788, SB202190 or BQ788 over a 3-day period using an osmotic pump...
September 2015: Seizure: the Journal of the British Epilepsy Association
Scott D Nei, Erica D Wittwer, Kianoush B Kashani, Erin N Frazee
Levetiracetam is a first-line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67-year-old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO...
August 2015: Pharmacotherapy
Emily M Laswell, Kasandra D Chambers, Danielle R Whitsel, Kiran Poudel
New-onset refractory status epilepticus (NORSE) is defined as a sudden onset of refractory status epilepticus in patients who do not have a history of epilepsy. It is a neurologic emergency, and determining the underlying etiology is an important factor for effectively managing and predicting the prognosis of NORSE. We describe the case of a 28-year-old woman who was hospitalized with NORSE secondary to an unknown etiology. She did not respond to traditional anticonvulsant therapy, including benzodiazepines, fosphenytoin, propofol, and levetiracetam...
June 2015: Pharmacotherapy
Revital Sheinberg, Eli Heyman, Zahi Dagan, Ilan Youngster, Elkana Kohn, Revital Gandelman-Marton, Matitiahu Berkovitch
BACKGROUND: Levetiracetam is used as adjunctive therapy in various types of seizures. Studies evaluating the effect of levetiracetam on children with refractory epilepsy are scarce. The aim of this study was to evaluate the correlation between serum concentration of levetiracetam and either efficacy or tolerability in children with refractory epilepsy, and to determine the value of levetiracetam blood level monitoring. METHODS: Medical records of 50 children with refractory epilepsy treated with levetiracetam and regularly followed at Assaf Harofeh Medical Center were retrospectively reviewed...
June 2015: Pediatric Neurology
Kenneth R Kaufman, Viwek Bisen, Aphrodite Zimmerman, Anthony Tobia, Ram Mani, Stephen Wong
Levetiracetam (LEV) is a novel antiepileptic drug (AED) approved for the adjunctive treatment of generalized and partial seizures. LEV has no clinically significant drug interactions and has limited adverse effects. The psychiatric adverse effects of LEV include de novo psychosis, affective disorder, and aggression. LEV-induced suicidal behavior has been reported infrequently with a past history of affective disorders. The authors report an apparent dose/concentration-dependent LEV-induced de novo major depression with near fatal suicide attempt in a patient without prior history of affective disorder...
2013: Epilepsy & Behavior Case Reports
Girish S Naik, Rohit Kodagali, Binu S Mathew, Maya Thomas, Ratna Prabha, Vivek Mathew, Denise H Fleming
BACKGROUND: This study was a retrospective assessment of the therapeutic drug monitoring data collected for levetiracetam and lamotrigine from a clinical setting. The proportion of patients in relation to the therapeutic ranges for serum concentrations of lamotrigine and levetiracetam was estimated, and the influence of age and anticonvulsant comedications on their clearances were studied. METHODS: Information on levetiracetam (2011-2013) and lamotrigine (2008-2013) dose, trough concentration, age, sex, body weight, and anticonvulsant comedications prescribed was obtained from the therapeutic drug monitoring register and archived medical records...
August 2015: Therapeutic Drug Monitoring
Panagiota Nikolaou, Ioannis Papoutsis, Chara Spiliopoulou, Constantinos Voudris, Sotiris Athanaselis
A simple gas chromatographic method with mass spectrometry detection was developed and validated for the determination of lacosamide in human plasma. Lacosamide and the internal standard, levetiracetam-d6, were extracted from 200 μL plasma, by a solid-phase extraction through HF Bond Elut C18 columns, and derivatized using N-methyl-N-tert-butyldimethylsilyltrifluoroacetamide with 1% tert-butyldimethylsilylchloride in acetonitrile. The limit of quantification was found to be 0.20 μg/mL and the assay was linear up to 20...
January 2015: Journal of Separation Science
Alberto M Cappellari, Dario Cattaneo, Emilio Clementi, Alessandra Kustermann
We report a 36-year-old pregnant patient with subtherapeutic trough plasma levels of levetiracetam (LVT) and a breakthrough nocturnal seizure while assuming 3 times a day dosing of the drug. An intensive pharmacokinetic study was performed from immediately before to 11 hours after the morning LVT dose administration and suggested that the patient was not adequately exposed to the drug during the night. After changing the dosing of LVT to 4 times a day, the patient experienced no seizures and delivered a healthy newborn without complications...
June 2015: Therapeutic Drug Monitoring
Panagiota Nikolaou, Ioannis Papoutsis, Artemisia Dona, Chara Spiliopoulou, Sotiris Athanaselis
A sensitive and accurate gas chromatography-mass spectrometric method was developed and validated for the simultaneous determination of levetiracetam and lamotrigine in whole blood. A solid-phase extraction (SPE) procedure using HF Bond Elut C18 columns followed by derivatization using N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide (MTBSTFA) with 1% tert-butyldimethylsilyl chloride (TBDMSCl) was used. In this assay, levetiracetam-d6 was used as internal standard. Limits of detection and quantification were 0...
January 2015: Journal of Pharmaceutical and Biomedical Analysis
Shaza Deeb, Denise A McKeown, Hazel J Torrance, Fiona M Wylie, Barry K Logan, Karen S Scott
In recent years, there has been a growth in reports of antiepileptic drugs (AEDs) being misused on their own or in combination with other drugs of abuse in a variety of toxicological case types such as drug abuse, suicide, overdose and drug facilitated crime. To our knowledge, there are no simultaneous quantification methods for the analysis of the most commonly encountered AEDs in postmortem whole blood and clinical plasma/serum samples at the same time. A simple, accurate and cost-effective liquid chromatography-tandem mass spectrometric (LC-MS-MS) method has been developed and validated for the simultaneous quantification of carbamazepine (CBZ) and its metabolite CBZ-10,11-epoxide, eslicarbazepine acetate, oxcarbazepine and S-licarbazepine as a metabolite, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, phenobarbital, phenytoin and its metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin, retigabine (ezogabine) and its metabolite N-acetyl retigabine, rufinamide, stiripentol, topiramate, tiagabine, valproic acid, vigabatrin and zonisamide in postmortem whole blood, serum and plasma which would be suitable for routine forensic toxicological analysis and therapeutic drug monitoring...
October 2014: Journal of Analytical Toxicology
Sara Baldelli, Dario Cattaneo, Luciana Giodini, Lorena Baietto, Giovanni Di Perri, Antonio D'Avolio, Emilio Clementi
BACKGROUND: Therapeutic drug monitoring (TDM) of antiepileptic drugs is widely used in clinical practice to optimise therapy, but it is limited by technical problems and cost considerations. The aim of the present study was: 1) to validate a chromatographic method for the concomitant determination of levetiracetam, lamotrigine, ethosuximide, felbamate, rufinamide, zonisamide and monohydroxycarbamazepine; 2) to develop it for dried plasma spot (DPS) assessing its reliability against the classical determination from plasma; and 3) test its clinical application...
February 2015: Clinical Chemistry and Laboratory Medicine: CCLM
Matthew D Krasowski, Gwendolyn A McMillin
In the past twenty-one years, 17 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are clobazam, ezogabine (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug monitoring is often used in the clinical dosing of the newer anti-epileptic drugs. The drugs with the best justifications for drug monitoring are lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide...
September 25, 2014: Clinica Chimica Acta; International Journal of Clinical Chemistry
Lisa C Garrity, Michele Turner, Shannon M Standridge
The use of levetiracetam for the treatment of epilepsy in women of childbearing age has increased as more evidence of teratogenicity of other broad-spectrum antiepileptic medications becomes available. Levetiracetam appears to be associated with a low incidence of major congenital malformations based on data from pregnancy registries. Major pregnancy-related changes in the pharmacokinetics of levetiracetam have been described in several case series, demonstrating a role for careful therapeutic drug monitoring of levetiracetam in pregnant patients...
July 2014: Pharmacotherapy
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