title: Assessment of CYP450 genetic variability effect on methadone dose and tolerance.
abstract: OBJECTIVE
  Methadone dose is related to treatment success in individuals under methadone maintenance treatment (MMT). We constructed a gene matrix using previously identified genetic polymorphisms in CYP450 and determined their genetic influence on methadone dose or tolerance.
  
  
  METHODS
  The allelic combinations of CYP450 genetic variants (two from CYP2C19, four from CYP2B6 and five from CYP3A4) were analyzed in 366 MMT heroin dependent patients as possible determinants of methadone dose and tolerance using analysis of covariance.
  
  
  RESULTS
  Methadone dose (p = 0.007) and tolerance (p = 0.06) were mainly influenced by CYP2C19 gene dose. Moreover, dominant influence of the CYP2C19 gene dose on methadone dose and tolerance was only found among MMT patients with negative urine morphine test results, but not among those with positive results.
  
  
  CONCLUSIONS
  The findings suggest that CYP2C19 gene dose may serve as a potential indicator for assessing methadone dose and tolerance in MMT patients.
authors: Division of Biostatistics & Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors: Hui-Ju
authors: HJ
authors: Tsai
authors: Sheng-Chang
authors: SC
authors: Wang
authors: Sheng-Wen
authors: SW
authors: Liu
authors: Ing-Kang
authors: IK
authors: Ho
authors: Yao-Sheng
authors: YS
authors: Chang
authors: Yu-Ting
authors: YT
authors: Tsai
authors: Keh-Ming
authors: KM
authors: Lin
authors: Yu-Li
authors: YL
authors: Liu
mesh_terms: D000328:Adult; D000483:Alleles; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D054316:Biomarkers, Pharmacological; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004361:Drug Tolerance / Q000235:genetics; D005260:Female; D006556:Heroin Dependence / Q000188:drug therapy / Q000235:genetics* / Q000652:urine; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009020:Morphine / Q000652:urine; D020641:Polymorphism, Single Nucleotide
chemical_list: D000701:Analgesics, Opioid; D054316:Biomarkers, Pharmacological; D009020:Morphine; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D008691:Methadone
keywords: CYP2B6; CYP2C19; CYP3A4; dosage matrix; dose; methadone