Pharmacogenomics of Oxcarbazepine in the Treatment of Epilepsy

Abstract

Oxcarbazepine (OXC) is one of the preferred drugs for partial seizures and generalized tonic-clonic seizures. However, clinical studies have found that there are considerable differences among different populations in OXC therapeutic efficacy or safety that result from the function changes of metabolic enzymes, transporters and other receptors involved in pharmacokinetics and pharmacodynamics in vivo. The authors collected all the information on the clinically reported associations between variants of common genes (e.g., UGT1A9, HLA-B, ABCB1) and OXC. In conclusion, these associations based on variants are beneficial for adjusting the medication regimen, which could be useful for individualized treatment with OXC.

Plain language summary

As a new-generation aromatic antiepileptic drug, oxcarbazepine (OXC) is often used for epilepsy treatment. It is known that when OXC is absorbed, it is reduced to an active metabolite in the liver and enters the brain through the blood circulation to play an antiepileptic role. Therefore, the variations of proteins participating in the process, including drug metabolic enzymes, transporters, drug targets and other receptors, have an effect on the efficacy and safety of OXC in vivo. In this study, the associations of some variants of common genes with OXC are summarized to provide epileptic patients an appropriate dose of OXC or reduce the risk of OXC-induced toxicity, which are in favor of personalized OXC treatment for patients with epilepsy.

Tweetable abstract

Pharmacogenomics of oxcarbazepine have attracted more and more attention. The authors summarized the information for the genetic variants of HLA-B, HLA-A, HLA-DRB1, ABCB1, ABCC2, SCN1A, UGT1A9, UGT2B7 and GABRA1 genes that affect OXC treatment outcomes and safety for patients with epilepsy.

Keywords::

• epilepsy
• genetic variants
• oxcarbazepine
• treatment efficacy

Author contributions

Y Yuan: designed the work, wrote the manuscript, acquired funding; S Zhang: searched the literature, assisted in writing; Y Yuan: assisted in writing and editing; X Yan: reviewed, edited; L Zhang: reviewed, edited; YW Ran: edited.

Financial & competing interests disclosure

This project is supported by the Medical Science and Technology Joint Construction Project of Henan Province (no. 2018020202). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This project is supported by the Medical Science and Technology Joint Construction Project of Henan Province (no. 2018020202). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.