CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Natasa Djordjevic
  • Dragana Dragas Milovanovic
  • Marija Radovanovic
  • Ivan Radosavljevic
  • Slobodan Obradovic
  • Mihajlo Jakovljevic
  • Dragan Milovanovic
  • Jasmina R Milovanovic
  • Slobodan Jankovic
Externa organisationer
  • University of Kragujevac
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)439-45
TidskriftEuropean Journal of Clinical Pharmacology
Volym72
Utgivningsnummer4
StatusPublished - 2016 apr
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa