ABCB1 Polymorphism Is Associated with Higher Carbamazepine Clearance in Children

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