ABCB1 C3435T, G2677T/A and C1236T variants have no effect in eslicarbazepine pharmacokinetics

• Published in: Biomedicine & pharmacotherapy Vol. 142; p. 112083
• Main Authors: Zubiaur, Pablo, del Peso-Casado, Miriam, Ochoa, Dolores, Enrique-Benedito, Teresa, Mejía-Abril, Gina, Navares, Marcos, Villapalos-García, Gonzalo, Román, Manuel, Abad-Santos, Francisco, Ovejero-Benito, María Carmen
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2021; Elsevier
• Subjects: Adult; Anti-epileptic drugs; Anticonvulsants - adverse effects; Anticonvulsants - pharmacokinetics; ATP Binding Cassette Transporter, Subfamily B - genetics; Cross-Over Studies; Dibenzazepines - adverse effects; Dibenzazepines - pharmacokinetics; Female; Genotype; Humans; Male; Middle Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; Racial Groups; Sex Factors; Young Adult; Anti-epileptic drugs; Pharmacogenetics
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.112083

Eslicarbazepine acetate is a third-generation anti-epileptic prodrug quickly and extensively transformed to eslicarbazepine after oral administration. Reduction in seizure frequency in patients managed with eslicarbazepine is only partial in the majority of patients and many of them suffer considerable ADRs that require a change of treatment. The P-glycoprotein, encoded by the ABCB1 gene, is expressed throughout the body and can impact the pharmacokinetics of several drugs. In terms of epilepsy treatment, this transporter was linked to drug-resistant epilepsy, as it conditions drug access into the brain due to its expression at the blood-brain barrier. Therefore, we aimed to investigate the impact of three ABCB1 common polymorphisms (i.e., C3435T, or rs1045642, G2677A or rs2032582 and C1236T or rs1128503) in the pharmacokinetics and safety of eslicarbazepine. For this purpose, 22 healthy volunteers participating in a bioequivalence clinical trial were recruited. No significant relationship was observed between sex, race and ABCB1 polymorphism and eslicarbazepine pharmacokinetic variability. In contrast, ABCB1 C1236T C/C diplotype was significantly related to the occurrence of ADRs: one volunteer with this genotype suffered dizziness, somnolence and hand paresthesia, while no other volunteer suffered any of these ADRs (p < 0.045). To the best of our knowledge, this is the first study published to date evaluating eslicarbazepine pharmacogenetics. Further studies with large sample sizes are needed to compare the results obtained here. [Display omitted] •ABCB1 variants had no effect in the pharmacokinetic variability of eslicarbazepine.•One volunteer with C1236T C/C diplotype suffered dizziness, somnolence and hand paresthesia.•No other association between ABCB1 variants safety variability was observed.•This is the first candidate gene pharmacogenetic study of eslicarbazepine published to date.