Feasibility of Using Oral Fluid for Therapeutic Drug Monitoring of Antiepileptic Drugs.

Abstract

Therapeutic drug monitoring (TDM) of antiepileptic drugs (AED) using blood is well established but limited by its invasiveness, accessibility, cost, interpretation errors, and related disturbances in protein binding. TDM using oral fluid (OF) could overcome these limitations. This paper provides a summary of the current evidence for using OF as a matrix to perform TDM of AEDs, as well as practical considerations. A literature search of MEDLINE, EMBASE, and the Cochrane Library was conducted on April 9, 2018 (and then updated on May 20, 2020) using all AEDs as keywords along with "oral fluid," "saliva," "salivary," "seizure," "epilepsy," "antiepileptic," and "anticonvulsant." A total of 18 relevant articles were found and included in this review. There is evidence to suggest that AED TDM using OF is feasible and that reference ranges can be calculated for the following drugs: carbamazepine, ethosuximide, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and valproic acid. For all other AEDs, there is either a lack of evidence on the feasibility of TDM using OF or the evidence indicates that TDM using OF is not feasible. Practical considerations should include the timing and method of OF collection (stimulated or unstimulated) due to their probable impact on the reliability of AED TDM. Using OF may improve the acceptability and accessibility and reduce the cost of AED TDM. Clinical implementation requires standardized collection protocols, more rigorously defined OF reference ranges, and further studies to determine the relevance to clinically important outcomes.