Journal List > Korean J Physiol Pharmacol > v.15(2) > 1025778

Kang, Park, Kim, Kim, and Jun: Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

Abstract

Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring.

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Fig. 1.
Relationship between pharmacokinetics and pharmacodynamics [1].
kjpp-15-67f1.tif
Table 1.
A common analytical method applied for major classic and new antiepileptic drugs
Classic AEDS New AEDs
Drugs Methods Drugs Methods
Carbamazepine FPIA; EMIT; GC; HPLC Felbamate HPLC-UV, –MS; GLC
Clobazam GC-EC, NP, MS; HPLC-UV Gabapentin HPLC; GC; LC-MS, -MS/MS
Clonazepam GC-EC, NP; MS; HPLC-UV Lamotrigine HPLC-UV; QMS immunoassay
Ethosuximide FPIA; EMIT; GC; HPLC Levetiracetam HPLC-UV; GC
Phenobarbital FPIA; EMIT; RIA; GC; HPLC Oxacarbazepine HPLC; GC
Phenytoin FPIAEMIT; GC; HPLC Tiagabine HPLC-EC, -UV; GC-MS; LC-MS
Primidone FPIAEMIT; GC; HPLC Topiramate FPIA; GC-FID, -NP, –MS; LC-MS
Sodium valproate FPIA EMIT; GC; HPLC Vigabatrin HPLC-FD; GC
    Zonisamide HPLC-UV; MEKC-DAD

HPLC, high-performance liquid chromatography; GC, gas chromatography; UV, ultraviolet; MS, mass spectrometry; GLC, gas liquid chromatography; EC, electron capture; NP, nitrogen-phosphorus; EMIT, enzyme-multiplied immunoassay technique; FPIA, fluorescence polarization immunoassays; CE, capillary electrophoresis; MS/MS, tandem mass spectrometry; FID, flame ionization detector; QMS, quantitative microsphere system; FD, fluorescence detector; MEKC-DAD, micellar electrokinetic chromatography-diode array detection.

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