title: The influence ofCYP2C8*3on carbamazepine serum concentration in epileptic pediatric patients.
abstract: The aim of the present study was to investigate the distribution ofCYP2C8variants*3and*5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). TheCYP2C8 *3and*5polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose inCYP2C8*3carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39vs. 15.46 ± 4.35 mg/kg;p= 0.5]. Dose-normalized serum concentration of carbamazepine was higher inCYP2C8*3(mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL,p= 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only inCYP2C8*3non carriers (r = 0.52,p= 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect ofCYP2C8 *3polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that theCYP2C8*3polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.
authors: Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: D D
authors: DD
authors: Milovanovic
authors: Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: J R
authors: JR
authors: Milovanovic
authors: Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: M
authors: M
authors: Radovanovic
authors: Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: I
authors: I
authors: Radosavljevic
authors: Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: S
authors: S
authors: Obradovic
authors: Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: S
authors: S
authors: Jankovic
authors: Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: D
authors: D
authors: Milovanovic
authors: Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors: N
authors: N
authors: Djordjevic
keywords: CYP2C8*3; Carbamazepine pharmacokinetics; Children; Population pharmacokinetics