Therapeutic Drug Monitoring of the Newer Antiepileptic Drugs

Abstract

The aim of the present review is to discuss the potential value of therapeutic drug monitoring (TDM) of the newer antiepileptic drugs (AEDs) felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, and zonisamide. Studies of the relationship between serum concentrations and clinical efficacy of these drugs are reviewed, and the potential value of TDM of the drugs is discussed based on their pharmacokinetic properties and mode of action. Analytical methods for the determination of the serum concentrations of these drugs are also briefly described. There are only some prospective data on the serum concentration-effect relationships, and few studies have been designed primarily to study these relationships. As TDM is not widely practiced for the newer AEDs, there are no generally accepted target ranges for any of these drugs, and for most a wide range in serum concentration is associated with clinical efficacy. Furthermore, a considerable overlap in drug concentrations related to toxicity and nonresponse is reported. Nevertheless, the current tentative target ranges for felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine (10-hydroxy-carbazepine metabolite), tiagabine, topiramate, vigabatrin, and zonisamide are 125 to 250 micromol/L, 70 to 120 micromol/L, 10 to 60 micromol/L, 35 to 120 micromol/L, 50 to 140 micomol/L, 50 to 250 nmol/L, 15 to 60 micromol/L, 6 to 278 micromol/L, and 45 to 180 micromol/L, respectively. Further systematic studies designed specifically to evaluate concentration-effect relationships of the new AEDs are urgently needed. Although routine monitoring in general cannot be recommended at present, measurements of some of the drugs is undoubtedly of help with individualization of treatment in selected cases in a particular clinical setting.

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

“…e Drug shows zero-order elimination kinetics. f References for reference ranges: felbamate [42,43], gabapentin [44], lacosamide [45], lamotrigine [46], levetiracetam [47], oxcarbazepine (10-hydroxycarbazepine metabolite) [48], pregabalin [2], stiripentol [49], tiagabine [50], topiramate [51], vigabatrin [23], zonisamide [52]. …”

“…Although the effect of hemodialysis on topiramate pharmacokinetics has not been reported, the low plasma protein binding of topiramate suggests that this drug should be effectively cleared by dialysis [19]. A reference range of 5–20 mg/L has been proposed for topiramate for epilepsy therapy [51]. The value of TDM of topiramate is mainly due to inter-individual variation in metabolism.…”

Appropriateness of digoxin level monitoring in a childrens hospital

“…These considerations mean that children are likely to benefit from therapeutic drug monitoring (TDM) for some drugs. TDM enables the clinician to adjust drug dosage according to the characteristics of the individual patient and this makes it an important tool to monitor safety and optimize therapy (Egberts et al, 2011;Johannessen et al, 2003;Kearns et al, 2003).…”

Enantioselective HPLC‐UV method for determination of eslicarbazepine acetate (BIA 2‐093) and its metabolites in human plasma

“…Moreover, considering that epilepsy is a neurological disease with high prevalence and high incidence in patients younger than 1 year and older than 75 years (Arroyo and Kramer, 2001;Jarrar and Buchhalter, 2003), the availability of an easy-to-use HPLC-UV method is also imperative to achieve individualized dosage regimens and to improve the overall clinical outcomes by monitoring plasma drug concentrations in these special populations (Perucca, 2000;Johannessen et al, 2003;Neels et al, 2004).…”