CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy
(2016) In European Journal of Clinical Pharmacology 72(4). p.45-439- 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... (More)
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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- author
- Djordjevic, Natasa ; Milovanovic, Dragana Dragas ; Radovanovic, Marija ; Radosavljevic, Ivan ; Obradovic, Slobodan ; Jakovljevic, Mihajlo LU ; Milovanovic, Dragan ; Milovanovic, Jasmina R and Jankovic, Slobodan
- publishing date
- 2016-04
- type
- Contribution to journal
- publication status
- published
- keywords
- Adolescent, Carbamazepine/pharmacokinetics, Child, Child, Preschool, Cytochrome P-450 CYP1A2/genetics, Epilepsy/drug therapy, Female, Genotype, Humans, Male, Polymorphism, Genetic/genetics
- in
- European Journal of Clinical Pharmacology
- volume
- 72
- issue
- 4
- pages
- 45 - 439
- publisher
- Springer
- external identifiers
-
- scopus:84954308407
- pmid:26762380
- ISSN
- 1432-1041
- DOI
- 10.1007/s00228-015-2006-9
- language
- English
- LU publication?
- no
- id
- 862239a1-6256-455e-8129-50393467f239
- date added to LUP
- 2018-09-01 22:48:38
- date last changed
- 2024-04-15 10:50:50
@article{862239a1-6256-455e-8129-50393467f239, abstract = {{<p>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.</p><p>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.</p><p>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).</p><p>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.</p>}}, author = {{Djordjevic, Natasa and Milovanovic, Dragana Dragas and Radovanovic, Marija and Radosavljevic, Ivan and Obradovic, Slobodan and Jakovljevic, Mihajlo and Milovanovic, Dragan and Milovanovic, Jasmina R and Jankovic, Slobodan}}, issn = {{1432-1041}}, keywords = {{Adolescent; Carbamazepine/pharmacokinetics; Child; Child, Preschool; Cytochrome P-450 CYP1A2/genetics; Epilepsy/drug therapy; Female; Genotype; Humans; Male; Polymorphism, Genetic/genetics}}, language = {{eng}}, number = {{4}}, pages = {{45--439}}, publisher = {{Springer}}, series = {{European Journal of Clinical Pharmacology}}, title = {{CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy}}, url = {{http://dx.doi.org/10.1007/s00228-015-2006-9}}, doi = {{10.1007/s00228-015-2006-9}}, volume = {{72}}, year = {{2016}}, }