Analysis Of Influencing Factors Of Plasma Concentration Of Oxcarbazepine Monotherapy In Children With Epilepsy

Abstract

Purpose: The aim of this study was to investigate the factors affecting the plasma concentration of oxcarbazepine (OXC) monotherapy in children with epilepsy. Methods: We recruited 125 children with epilepsy who received OXC monotherapy. 27 single nucleotide polymorphisms were detected by MassARRAY genotyping technology to evaluate the influence of related factors on the plasma concentration of OXC monotherapy. The plasma concentration of 10-hydroxycarbamazepine (MHD), the main active metabolite of OXC, was determined by high performance liquid chromatography (HPLC). Results: The weight was found to be associated with concentration-dose ratio and maintenance dose. The duration of seizure was found to be associated with concentration-dose ratio. Carriers of the UGT1A4 rs2011425 mutant allele A or G had higher MHD plasma concentration than wild homozygous TT type. Carriers of the UGT2B15 rs1902023 mutant allele C had higher plasma concentration than wild homozygous AA types. The concentration-dose ratio of patients with ABCB1 rs1045642 mutation homozygous GG type is higher than heterozygous AG type. The concentration-dose ratio of patients with CACNA1H rs2753325 heterozygous AG type was higher than mutant homozygous GG type. We established a concentration prediction equation for OXC monotherapy in children with epilepsy. Conclusion: This study clarified the association of weight, duration of seizure, and gene polymorphisms of UGT1A4 rs2011425, UGT2B15 rs1902023, ABCB1 rs1045642 and CACNA1H rs2753325 with MHD plasma concentration. The concentration prediction equation of OXC monotherapy in children with epilepsy was constructed, which provides a reference for individualized clinical administration.