Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

Abstract

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.

Therapeutic Drug Monitoring of Classical and Newer Anticonvulsants

“…These relatively more expensive and more complex testing mechanisms relegate testing to large hospital laboratories or a reference laboratory for analysis, and smaller local laboratories are unable to offer these tests. Highperformance liquid chromatography with tandem mass spectrometry gives very high sensitivity and selectivity in quantifying gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin and topiramate [30]. These chromatographic methods have the additional advantage of being able to measure multiple AEDs concurrently.…”

“…Additional detailed information can be found in several review articles that include those about the newer anti-epileptic medications from 2010 [30], a combination of new and old anti-epileptic medications from 2004 [31], and a review of new anti-epileptic drugs from the (2007) 8th Eilat Conference [32]. Chemical structures of the drug are shown in Fig.…”

“…No commonly agreed upon reference levels for the drug are described, but a suggested range is 5e10 mg/L (5e10 mg/mL) [30].…”

“…The proposed therapeutic range varies, with 20e200 ng/mL being more common [6,30], and comes from a study [120] where the average 1-hour post-dosing measurements of tiagabine in patients at the high and low therapeutic doses were 38 and 140 ng/mL, respectively. In this same study, trough levels were significantly lower; thus, most values would be expected to be at the lower end of the range.…”

Performances et stabilité du réactif QMS® lamotrigine sur CDx90® (ThermoFisherScientific)

“…La lamotrigine est un médicament utilisé dans le traitement de d'épilepsie [1][2][3][4][5] et des troubles bipolaires. Il a été mis sur le marché en 1996 en France par Glaxo Smith Kline (Lamictal ® ).…”