ABCB1 Polymorphism Is Associated with Higher Carbamazepine Clearance in Children

The aim of our study was to investigate the role of <i>ABCB1</i> polymorphism in the pharmacokinetics of carbamazepine (CBZ) in children. The study enrolled 47 Serbian pediatric epileptic patients on CBZ treatment. Genotyping for <i>ABCB1</i> 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. <i>ABCB1</i> 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 × <i>ABCB1</i> + 0.0176 × CYP1A2 + 0.000151 × DD where SEX has a value of 1 if male and 0 if female, <i>ABCB1</i> has a value of 1 if C-G-C/T-T-T and 0 if any other <i>ABCB1</i> 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 <i>ABCB1</i> 1236T-2677T-3435T haplotype is associated with an increased clearance of CBZ in pediatric epileptic patients.