Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

Department of Pathology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, RCP 6233, Iowa City, IA 52242.
Pharmaceuticals 06/2010; 3(6):1909-1935. DOI: 10.3390/ph3061909
Source: PubMed


In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy.

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    • "body. The most important of these substances include salicylates, antiepileptic drugs, antidepressants and hepatotoxic drugs (benzodiazepines, barbiturates) (Pradoa et al., 2005; Hancu et al., 2007; Krasowski, 2010; Szoko and Tabi, 2010; Vuignier et al., 2010; Fan et al., 2012; Madej, 2012), as well as many illegally used substances such as opiates, methadone, LSD, cocaine and amphetamine (Meng et al., 2006; Sekhon, 2011; Cruces-Blanco and García-Campana, 2012). CE also allows one to specify the distribution coefficient (log P), which is the exponent of the lipophilicity (P) of the drug owing to the tendency of water to the surrounding nonpolar molecules. "
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    ABSTRACT: Capillary electrophoresis (CE) comprises a group of techniques used to separate chemical mixtures. Analytical separation is based on different electrophoretic mobilities, thereby allowing qualitative and quantitative evaluations to be made. The application of CE in medical science, especially in toxicological studies, is developing rapidly because of the short time required for analysis and its high sensitivity, selectivity and ability to determine substances of an acidic, alkaline and neutral character. This review focuses on the possibility of applying CE in toxicological analysis. Advances in different CE analyses and detection techniques connected with this method are described. Copyright © 2014 John Wiley & Sons, Ltd.
    Biomedical Chromatography 11/2014; 28(11). DOI:10.1002/bmc.3234 · 1.72 Impact Factor
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    • "The concentra - tions tested were 5 , 10 and 20 ␮g / ml for RFM and PGB , and 10 , 20 , 40 ␮g / ml for ZNS , which are in the range of clinical plasma levels ( Perucca et al . , 2008 ; Krasowski , 2010 ) . There was no significant difference between apical and basolateral concentrations after exposing LLC - MDR1 cell monolayers to RFM ( Fig . 2 ) , PGB ( Fig . "
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    ABSTRACT: Objective Epilepsy is resistant to treatment with antiepileptic drugs (AEDs) in about one third of epilepsy patients. AED export by P-glycoprotein (Pgp) overexpressed in the blood-brain barrier may contribute to AED resistance. The Pgp transport status of many of the recently approved AEDs remains unknown. We investigated whether several new AEDs--zonisamide (ZNS), pregabalin (PGB), and rufinamide (RFM)--are human Pgp substrates. Methods MDCKII and LLC-PK1 cells transfected with the human MDR1 gene, which encodes the Pgp protein, were used in concentration equilibrium transport assays (CETA) to determine the substrate status of ZNS, PGB, and RFM. For each drug, an equal concentration was added to apical and basal chambers, and the concentration in both chambers was measured up to 4 hours. Results RFM, ZNS, and PGB were not transported by MDR1-transfected cells from basolateral to apical sides in CETA. Conclusions ZNS, RFM, and PGB are not substrates of human Pgp. These data suggest that resistance to these drugs may not be attributed to increased Pgp activity in resistant patients.
    Epilepsy research 03/2014; 108(3). DOI:10.1016/j.eplepsyres.2014.01.011 · 2.02 Impact Factor
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    • "Moreover, there is no clear correlation between TDM and clinical efficacy or adverse effects of the newer AEDs. Thus, TDM has little, if any, clinical role in the manage-ment of epileptic patients on newer AEDs (Krasowski, 2010; Neels et al., 2004; Striano et al., 2008). "
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    ABSTRACT: In epilepsy, therapeutic drug monitoring (TDM) could aid in individualizing dosage regimen and ascertaining compliance on anti-epileptic drugs (AEDs). The aim of this study was to survey the requests for TDM of AEDs to determine drugs involved, observed concentrations, reasons for requests and action undertaken. TDM requests for AEDs were surveyed at a university hospital in Oman from January 2006 to December 2009. A total of 151 patients with 354 TDM requests were collected. These requests were for valproic acid (46.9%), phenytoin (26.8%), carbamazepine (25.4%) and phenobarbital (0.8%). 50, 37 and 13% of all reported concentrations were below, within and above therapeutic range, respectively. For majority of the subjects (70%), there were no clear reasons for plasma concentrations to lie outside the therapeutic range. No change in the drug therapy/dosing was required subsequent to the TDM reports in 42.7% of the cases. Emergency department was the main unit requesting TDM (63.8%) and TDM was mostly indicated for an increase in the seizures frequency on the same day (62.7%). This study provides an overview of the specific requests for TDM of AEDs in routine clinical practice which might help in auditing and improving this service for optimal utilization.
    African journal of pharmacy and pharmacology 7(2):58-62. DOI:10.5897/AJPP12.1203 · 0.84 Impact Factor
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