Disease Information

General Information of the Disease (ID: DIS00261)

• Name: Epilepsy
• ICD: ICD-11: 8A60

Type(s) of Resistant Mechanism of This Disease

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Carbamazepine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Molecule Alteration: SNP; rs1128503
• Resistant Drug: Carbamazepine
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: ABCB1 polymorphisms were previously demonstrated to be associated with the metabolism and resistance of carbamazepine (CBZ) in epilepsy. ABCB1 rs1045642 and rs2032582 polymorphisms were associated with CBZ metabolism for epilepsy, and rs1128503 was related to carbamazepine resistance.

Oxcarbazepine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxcarbazepine
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: In patients with oxcarbazepine (OXC)-resistant epilepsy, the brain tissue expression of ABCB1 mRNA was found to be inversely correlated with brain levels of 10,11-dihydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide, the active metabolite of OXC, indicating that Pgp may play a role in the pharmacoresistance to OXC by causing insufficient concentrations of its active metabolite at neuronal targets.

Phenytoin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Phenytoin
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Comparing phenytoin brain/plasma ratio in mdr1 knockout mice with this ratio in mice with kainate-induced overexpression of Pgp indicated that Pgp can affect up to about 70% of phenytoin brain uptake. In epileptic rats, van Vliet et al reported decreased brain levels of phenytoin that were restricted to brain regions with increased expression of Pgp, which could be counteracted by inhibiting Pgp.

References

• Ref 1: Association of ABCB1 polymorphisms with carbamazepine metabolism and resistance in epilepsy: A meta-analysis .Epilepsy Res. 2021 Nov;177:106785. doi: 10.1016/j.eplepsyres.2021.106785. Epub 2021 Oct 7. 10.1016/j.eplepsyres.2021.106785
• Ref 2: Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options .Pharmacol Rev. 2020 Jul;72(3):606-638. doi: 10.1124/pr.120.019539. 10.1124/pr.120.019539