Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Abstract

Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.

Dried Blood Spot Analysis to Assess Medication Adherence and to Inform Personalization of Treatment

“…Dried blood spot analysis to assess medication adherence & to inform personalization of treatment Perspective Epilepsy Antiepileptic drugs (AED) are the mainstay for the control of seizures in the management of epilepsy [64]. Measuring AEDs in serum or plasma as an aid to personalising drug therapy is now a well established practice in the treatment of epilepsy [65].…”

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

“…Specific antiepileptic drugs for which oral fluid provides a good alternative include carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. For valproic acid on the other hand, this approach is not useful 12 .…”

“…In addition, oral fluid analysis is also prone to oral contamination. Therefore, sampling should be performed immediately before drug intake or after an adequate 'wash-out' period 12 . Furthermore, blood contamination of the oral fluid caused by leakage from the oral mucosa as a result of microinjuries, such as burns or abrasions and due to gingivitis and periodontitis or even following regular mouth hygiene, might compromise analyte quantitation in oral fluid.…”

Detection of illicit drugs in oral fluid from drivers as biomarker for drugs in blood

“…The use of oral fluid for diagnostic purposes is increasing; it can be used for the diagnosis of several diseases [1,2], to monitor exposure to chemicals [3,4], monitor therapeutic use of some drugs [5,6], and to detect recent use of illicit drugs [7][8][9]. On-site screening devices based on immunological methods are available for rapid screening of drugs in oral fluid [10,11], and positive findings are often used as reason for taking blood samples for quantification of drugs, particularly from drivers suspected for driving under the influence of drugs (DUID) [12].…”