<em>ABCB1</em> Polymorphism Is Associated with Higher Carbamazepine Clearance in Children

Background/Objectives: The aim of our study was to investigate the role of ABCB1 polymorphism in pharmacokinetics of carbamazepine (CBZ) in children. Methods: The study enrolled 47 Serbian pediatric epileptic patients on CBZ treatment. Genotyping for ABCB1 1236C&amp;lt;T (rs1128503), 2677G&amp;lt;A/T (rs2032582) and 3435C&amp;lt;T (rs1045642) was carried out using TaqMan method. Steady-state CBZ serum concentrations were available from the previous study, determined by high pressure liquid chromatography (HPLC) method. NONMEM software and one-compartment model were used for pharmacokinetic analysis. Results: ABCB1 1236C&amp;lt;T, 2677G&amp;lt;A/T and 3435C&amp;lt;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). Conclusions: The presence of ABCB1 1236T-2677T-3435T haplotype is associated with increased clearance of CBZ in pediatric epileptic patients.