THE INFLUENCE OF CYP2C8*3 ON CARBAMAZEPINE SERUM CONCENTRATION IN EPILEPTIC PEDIATRIC PATIENTS
Milovanovic DD, Milovanovic JR, Radovanovic M, Radosavljevic I, Obradovic S, Jankovic S, Milovanovic D, Djordjevic N
*Corresponding Author: M.D., Ph.D., Associate Professor, Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34 000 Kragujevac, Serbia. Tel: +381-34-306-800, ext 223. Fax: +381-34-306-800. E-mail: natashadj2002@yahoo.com
page: 21
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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.



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