CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy
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PURPOSE: The purpose of this study is to investigate the effect of two of the most important functional CYP1A2 variations -3860G > A and -163C > A on carbamazepine pharmacokinetics in Serbian pediatric epileptic patients.
METHODS: The study involved 40 Serbian pediatric epileptic patients on steady-state carbamazepine treatment. Genotyping for -3860G > A and -163C > A was carried out using PCR-RFLP method, and carbamazepine plasma concentrations were determined by high pressure liquid chromatography (HPLC) method. For pharmacokinetic analysis, NONMEM software with implementation of ADVAN 1 subroutine was used.
RESULTS: CYP1A2 polymorphism -163C > A was found at the frequency of 65.0 %, while -3860G > A was not detected. The correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in carriers of -163C/C and C/A genotypes (r = 0.68, p = 0.0004). The equation that described population clearance (CL) was CL (l/h) = 0.176 + 0.0484 * SEX + 0.019 * CYP1A2 + 0.000156 * DD, where SEX has a value of 1 if male and 0 if female, CYP1A2 has a value of 1 if -163A/A and 0 if -163C/C or C/A, and DD is the total carbamazepine daily dose (mg/day).
CONCLUSIONS: CYP1A2 -163A/A genotype influence carbamazepine pharmacokinetics. In addition to sex and total carbamazepine daily dose, -163C > A CYP1A2 polymorphism should be considered as a predictor of carbamazepine clearance.
|Tidskrift||European Journal of Clinical Pharmacology|
|Status||Published - 2016 apr|
|Peer review utförd||Ja|