CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy
European journal of clinical pharmacology(2016)
摘要
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.
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关键词
CYP1A2 genotype,Carbamazepine,Children,Pharmacokinetics
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