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 download article in pdf format
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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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