The influence of CYP2C8*3 on carbamazepine serum concentration in epileptic pediatric patients
Author:
Milovanovic DD1, Milovanovic JR1, Radovanovic M2, Radosavljevic I3, Obradovic S2, Jankovic S1, Milovanovic D1, Djordjevic N1
Affiliation:
1. Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia 2. Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Serbia 3. Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Serbia
Abstract
Abstract
The aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *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). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*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 in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.
Publisher
Walter de Gruyter GmbH
Subject
Genetics (clinical),Genetics
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