Informacja

Drogi użytkowniku, aplikacja do prawidłowego działania wymaga obsługi JavaScript. Proszę włącz obsługę JavaScript w Twojej przeglądarce.

Przeglądasz jako GOŚĆ
Tytuł pozycji:

Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin.

Tytuł :
Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin.
Index Terms :
Neurologie
Adolescent
Adult
Aged
Alleles
Amino Acid Sequence
Anticonvulsants -- administration & dosage -- therapeutic use
Aryl Hydrocarbon Hydroxylases -- genetics
Base Sequence
Brain -- metabolism
Carbamazepine -- administration & dosage -- therapeutic use
Child
Child, Preschool
Cohort Studies
Epilepsy -- drug therapy
Exons -- genetics
Female
Genetic Markers -- genetics
Genotype
Humans
Infant
Introns -- genetics
Male
Middle Aged
Molecular Sequence Data
Nerve Tissue Proteins -- genetics
Phenytoin -- administration & dosage -- therapeutic use
Polymorphism, Genetic -- genetics
Sodium Channels -- genetics
info:eu-repo/semantics/article
info:ulb-repo/semantics/articlePeerReview
info:ulb-repo/semantics/openurl/article
Wydawca :
2005-04
Dodane szczegóły :
Tate, Sarah K
Depondt, Chantal
Sisodiya, Sanjay M
Cavalleri, Gianpiero L
Schorge, Stephanie
Soranzo, Nicole
Thom, Maria
Sen, Arjune
Shorvon, S.
Sander, Josemir W
Wood, Nicholas W
Goldstein, David B
Typ dokumentu :
Zasób elektroniczny
URL :
http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/108257">http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/108257
http://worldcat.org/search?q=on:EQY+http://difusion-oai.ulb.ac.be/oai/request+DCG_ENTIRE_REPOSITORY+CNTCOLL">http://worldcat.org/search?q=on:EQY+http://difusion-oai.ulb.ac.be/oai/request+DCG_ENTIRE_REPOSITORY+CNTCOLL
Dostępność :
Open access content. Open access content
1 full-text file(s): info:eu-repo/semantics/restrictedAccess
Pozostałe numery :
EQY oai:dipot.ulb.ac.be:2013/108257
803483231
Źródło wspomagające :
UNIV LIBR DE BRUXELLES
From OAIster®, provided by the OCLC Cooperative.
Numer akcesji :
edsoai.ocn803483231
Zasób elektroniczny
Phenytoin and carbamazepine are effective and inexpensive anti-epileptic drugs (AEDs). As with many AEDs, a broad range of doses is used, with the final "maintenance" dose normally determined by trial and error. Although many genes could influence response to these medicines, there are obvious candidates. Both drugs target the alpha-subunit of the sodium channel, encoded by the SCN family of genes. Phenytoin is principally metabolized by CYP2C9, and both are probable substrates of the drug transporter P-glycoprotein. We therefore assessed whether variation in these genes associates with the clinical use of carbamazepine and phenytoin in cohorts of 425 and 281 patients, respectively. We report that a known functional polymorphism in CYP2C9 is highly associated with the maximum dose of phenytoin (P = 0.0066). We also show that an intronic polymorphism in the SCN1A gene shows significant association with maximum doses in regular usage of both carbamazepine and phenytoin (P = 0.0051 and P = 0.014, respectively). This polymorphism disrupts the consensus sequence of the 5' splice donor site of a highly conserved alternative exon (5N), and it significantly affects the proportions of the alternative transcripts in individuals with a history of epilepsy. These results provide evidence of a drug target polymorphism associated with the clinical use of AEDs and set the stage for a prospective evaluation of how pharmacogenetic diagnostics can be used to improve dosing decisions in the use of phenytoin and carbamazepine. Although the case made here is compelling, our results cannot be considered definitive or ready for clinical application until they are confirmed by independent replication.
Journal Article
Research Support, Non-U.S. Gov't
info:eu-repo/semantics/published

Ta witryna wykorzystuje pliki cookies do przechowywania informacji na Twoim komputerze. Pliki cookies stosujemy w celu świadczenia usług na najwyższym poziomie, w tym w sposób dostosowany do indywidualnych potrzeb. Korzystanie z witryny bez zmiany ustawień dotyczących cookies oznacza, że będą one zamieszczane w Twoim komputerze. W każdym momencie możesz dokonać zmiany ustawień dotyczących cookies