title: [Influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide metabolism using oligonucleotide genotyping microarray].
abstract: OBJECTIVE
  To investigate the influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide.
  
  
  METHODS
  An oligonucleotide microarray was designed and fabricated to genotype the CYP2C9 accurately and quickly. 137 healthy volunteers were genotyped with the array to investigate the frequency of CYP2C9 functional SNPs. Moreover, 1 homozygous mutant, 9 heterozygous and 10 wild-genotypes subjects in the assay were selected randomly and sequenced directly. After orally taking tolbutamide, blood samples and urine samples were collected, and their pharmacokinetics was studied with HPLC.
  
  
  RESULTS
  CYP2C9 *1/*3 were found in 9 of 137 volunteers, CYP2C9 *3/*3 in only one, others were all CYP2C9 *1/*1 wild types. CYP2C9 *2, CYP2C9 *4 and CYP2C9 *5 alleles were not detected. Direct sequencing of the purified PCR products of the heterozygotes, mutant homozygotes and ten wild type individuals gave a corresponding result to that genotyped by microarray. Pharmacokinetic outcome showed that the individuals with CYP2C9 *1/*3 or CYP2C9 *3/*3 had slower metabolic elimination of tolbutamide than those with CYP2C9 *1/*1.
  
  
  CONCLUSIONS
  CYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of tolbutamide. Pharmacogenomic study will be helpful in guiding rational and individualized medication. Key words: tolbutamide; cytochrom P450 CYP2C9; allele; single nucleotide polymorphism; genotyping
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Si-yuan
authors.initials: SY
authors.lastname: Wen
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Fei
authors.initials: F
authors.lastname: Pei
authors.forename: Sheng-qi
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D014044:Tolbutamide / Q000493:pharmacokinetics*
chemical_list: D014044:Tolbutamide; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases