多态性与儿童更高的卡马西平清除率相关。

Polymorphism Is Associated with Higher Carbamazepine Clearance in Children.

作者信息

Djordjevic Natasa, Cukic Jelena, Dragas Milovanovic Dragana, Radovanovic Marija, Radosavljevic Ivan, Vuckovic Filipovic Jelena, Obradovic Slobodan, Baskic Dejan, Milovanovic Jasmina R, Jankovic Slobodan, Milovanovic Dragan

机构信息

Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34 000 Kragujevac, Serbia.

Public Health Institute, Nikole Pasica 1, 34 000 Kragujevac, Serbia.

出版信息

Pediatr Rep. 2025 Jan 16;17(1):10. doi: 10.3390/pediatric17010010.

DOI:10.3390/pediatric17010010

PMID:39846525

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11755583/

Abstract

The aim of our study was to investigate the role of polymorphism in the pharmacokinetics of carbamazepine (CBZ) in children. The study enrolled 47 Serbian pediatric epileptic patients on CBZ treatment. Genotyping for 1236C<T (rs1128503), 2677G<A/T (rs2032582) and 3435C<T (rs1045642) was carried out using the TaqMan method. Steady-state CBZ serum concentrations were available from our previous study, determined by high pressure liquid chromatography (HPLC). The NONMEM software and one-compartment model were used for pharmacokinetic analysis. 1236C<T, 2677G<A/T and 3435C<T variations were found at the frequencies of 47.9%, 48.9% and 52.1%, respectively. The equation that described population clearance (CL) was CL (L/h) = 0.175 + 0.0403 × SEX + 0.0332 × + 0.0176 × CYP1A2 + 0.000151 × DD where SEX has a value of 1 if male and 0 if female, has a value of 1 if C-G-C/T-T-T and 0 if any other diplotype, CYP1A2 has a value of 1 if -163A/A and 0 if -163C/C or C/A, and DD is the total CBZ daily dose (mg/day). The presence of the 1236T-2677T-3435T haplotype is associated with an increased clearance of CBZ in pediatric epileptic patients.

摘要

我们研究的目的是调查基因多态性在儿童卡马西平（CBZ）药代动力学中的作用。该研究纳入了47名接受CBZ治疗的塞尔维亚儿科癫痫患者。采用TaqMan方法对1236C<T（rs1128503）、2677G<A/T（rs2032582）和3435C<T（rs1045642）进行基因分型。稳态CBZ血清浓度来自我们之前的研究，通过高压液相色谱（HPLC）测定。使用NONMEM软件和单室模型进行药代动力学分析。发现1236C<T、2677G<A/T和3435C<T变异的频率分别为47.9%、48.9%和52.1%。描述群体清除率（CL）的方程为CL（L/h）=0.175 + 0.0403×性别 + 0.0332× + 0.0176×CYP1A2 + 0.000151×DD，其中如果是男性，性别取值为1，如果是女性取值为0；如果是C-G-C/T-T-T，取值为1，如果是其他双倍型取值为0；如果是-163A/A，CYP1A2取值为1，如果是-163C/C或C/A取值为0，DD是CBZ的每日总剂量（mg/天）。1236T-2677T-3435T单倍型的存在与儿科癫痫患者中CBZ清除率增加有关。