Asset Details
Do you wish to reserve the book?
Genetic Predictors of the Maximum Doses Patients Receive during Clinical Use of the Anti-Epileptic Drugs Carbamazepine and Phenytoin
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Genetic Predictors of the Maximum Doses Patients Receive during Clinical Use of the Anti-Epileptic Drugs Carbamazepine and Phenytoin
Do you wish to request the book?
Genetic Predictors of the Maximum Doses Patients Receive during Clinical Use of the Anti-Epileptic Drugs Carbamazepine and Phenytoin
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Genetic Predictors of the Maximum Doses Patients Receive during Clinical Use of the Anti-Epileptic Drugs Carbamazepine and Phenytoin
2005
Overview
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 α-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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Adult
/ Aged
/ Alleles
/ Anticonvulsants - administration & dosage
/ Anticonvulsants - therapeutic use
/ Aryl Hydrocarbon Hydroxylases - genetics
/ Carbamazepine - administration & dosage
/ Carbamazepine - therapeutic use
/ Child
/ Dosage
/ Epilepsy
/ Exons
/ Female
/ Genetics
/ Genotype
/ Humans
/ Infant
/ Male
/ NAV1.1 Voltage-Gated Sodium Channel
/ Nerve Tissue Proteins - genetics
/ Patients
/ Phenytoin - administration & dosage
