Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti-epileptic drugs

Kyoung Lok Min, Jae Yeoul Ryu, Min Jung Chang

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)


Anti-epileptic drugs (AEDs) have various pharmacokinetic profiles, inter-individual variabilities, high possibilities of drug-drug interactions and narrow therapeutic indices. To provide optimal treatment for patients, therapeutic drug monitoring (TDM) is necessary. However, TDM requires sufficient quantities of blood samples to measure drug concentrations. Therefore, TDM could be a burden, particularly in paediatric cases. A good alternative that overcomes these disadvantages is the dried blood spot (DBS) method, which is simple, convenient to use and less invasive, requiring a lower quantity of blood than traditional blood sampling methods. However, the DBS method is affected by haematocrit (Hct) levels to varying extents depending on the drug properties. In addition, different papers with varying characteristics are available for use when applying the DBS method. Therefore, it has not yet been applied to TDM in clinical practice. To achieve this, several steps are required, including method development, method validation and clinical validation. Currently, the development status of the DBS method is different for each AED and unclear. Therefore, we assessed the development status of the following 19 AEDs in 26 studies: lamotrigine, valproic acid, levetiracetam, phenytoin, topiramate, carbamazepine, carbamazepine epoxide, gabapentin, phenobarbital, pregabalin, clobazam, clonazepam, ethosuximide, felbamate, monohydroxycarbamazepine, nitrazepam, rufinamide, vigabatrin and zonisamide. Among them, carbamazepine, lamotrigine, topiramate and valproic acid have been developed such that they are nearly available for TDM. In addition, Whatman 903 Protein Saver Cards and concentration analysis by liquid chromatography with triple quadrupole mass spectrometer were used most often.

Original languageEnglish
Pages (from-to)215-236
Number of pages22
JournalBasic and Clinical Pharmacology and Toxicology
Issue number3
Publication statusPublished - 2019

Bibliographical note

Funding Information:
This research was supported by the Yonsei University Research Fund of 2018‐22‐0023.

Publisher Copyright:
© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology


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