Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-11-6
pubmed:abstractText
Riluzole is the only FDA approved drug for the treatment of amyotrophic lateral sclerosis. Riluzole is assumed to be mainly metabolized by the liver cytochrome CYP1A2 and by the extra-hepatic cytochrome CYP1A1. CYP1A2 and CYP1A1 genetic polymorphisms are known, but their relationship to riluzole metabolism in ALS patients has not been investigated. The aim of this study was to determine whether the polymorphisms of the CYP1A2 and the CYP1A1 genes in ALS patients are associated with riluzole metabolic profiles. Thirty-two patients with a diagnosis of probable or definite ALS and who were on riluzole, participated in the study. Trough and peak plasma riluzole levels were measured using analytical chromatography-mass spectrometry methods. Association of the genotypes of the SNPs spanning the CYP1A1 and CYP1A2 genes (including one SNP in the intergenic region) with mean riluzole peak and trough levels was studied using ANOVA and Tukey's HSD. The mean peak riluzole level was 202+/-111 ng/ml and mean trough level 54.3+/-37.5 ng/ml. Our data do not support any association of the four CYP1A1 and CYP1A2 polymorphisms with the riluzole metabolic profile. In conclusion, genetic variations in CYP1A1 and CYP1A2 genes do not seem to influence riluzole levels. Further work is needed to better understand the genetic regulation of CYP1A enzymes and their role in riluzole metabolism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1748-2968
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
305-9
pubmed:dateRevised
2009-11-17
pubmed:meshHeading
pubmed-meshheading:17852022-Adult, pubmed-meshheading:17852022-Aged, pubmed-meshheading:17852022-Aged, 80 and over, pubmed-meshheading:17852022-Amyotrophic Lateral Sclerosis, pubmed-meshheading:17852022-Analysis of Variance, pubmed-meshheading:17852022-Chromatography, High Pressure Liquid, pubmed-meshheading:17852022-Chromosomes, Human, Pair 5, pubmed-meshheading:17852022-Cytochrome P-450 CYP1A1, pubmed-meshheading:17852022-Cytochrome P-450 CYP1A2, pubmed-meshheading:17852022-Female, pubmed-meshheading:17852022-Genotype, pubmed-meshheading:17852022-Humans, pubmed-meshheading:17852022-Male, pubmed-meshheading:17852022-Mass Spectrometry, pubmed-meshheading:17852022-Middle Aged, pubmed-meshheading:17852022-Neuroprotective Agents, pubmed-meshheading:17852022-Pharmacogenetics, pubmed-meshheading:17852022-Polymorphism, Single Nucleotide, pubmed-meshheading:17852022-Riluzole
pubmed:year
2007
pubmed:articleTitle
Riluzole metabolism and CYP1A1/2 polymorphisms in patients with ALS.
pubmed:affiliation
Davee Department of Neurology and Clinical Neurosciences, Northwestern University Institute of Neuroscience, Chicago, Illinois 60611, USA. s-ajroud@md.northwestern.edu
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't