Pharmacokinetics and Pharmacogenetics of Carbamazepine in Children.

Although carbamazepine is one of the oldest anticonvulsant drugs, it is still heavily utilized for treatment of epilepsy in children. The aim of this article was to review the current knowledge about pharmacokinetics and pharmacogenetics of carbamazepine in children. The literature for this review was systematically searched for in the MEDLINE and SCINDEKS databases. Oral bioavailability of carbamazepine in children is about 75-85%, and it is approximately 75-85% bound to plasma proteins. Apparent volume of distribution is 1.2-1.9 l/kg and total clearance between 0.05 and 0.1 l/h/kg. Pharmacokinetics of carbamazepine in children is age and body weight dependent and highly variable due to influence of dosing regimen and co-medication. The current evidence on the importance of pharmacogenetics for carbamazepine efficacy and safety in children supports the association of PXR1B, HNF4a rs2071197, CYP1A21F, ABCC2 1249G>A, and PRRT2 c.649dupC with either pharmacokinetics or pharmacodynamics of carbamazepine. The importance of human leukocyte antigen (HLA) typing for prediction of adverse drug reactions to carbamazepine in children is also confirmed. Both genetic and environmental factors are responsible for shaping pharmacokinetics and pharmacodynamics of carbamazepine in children. To ensure safe and effective use of carbamazepine in this population, physicians should adjust dosing regimen according to existing pattern of genetic and environmental influences.