國家衛生研究院 NHRI:Item 3990099045/5818
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5818


    Title: CYP2B6 polymorphisms influence the plasma concentration and clearance of the methadone S-enantiomer
    Authors: Wang, SC;Ho, IK;Tsou, HH;Tian, JN;Hsiao, CF;Chen, CH;Tan, HK;Lin, L;Wu, CS;Su, LW;Huang, CL;Yang, YH;Liu, ML;Lin, KM;Chen, CY;Liu, SC;Wu, HY;Chan, HW;Tsai, MH;Lin, PS;Liu, YL
    Contributors: Division of Mental Health and Addiction Medicine;Division of Biostatistics and Bioinformatics
    Abstract: Methadone is a racemic compound composed of the R-form and S-form enantiomers. The drug is usually used in maintenance therapy for the heroin-addicted patients. In our previous study, we found that the cytochrome P-450 (CYP) isozyme 2B6 preferentially metabolizes the S-methadone enantiomer. We thus tested whether CYP2B6 gene polymorphisms had any influence on the concentration or clearance of methadone. Ten single nucleotide polymorphisms within this gene region were evaluated in 366 patients undergoing methadone maintenance for at least 3 months. The plasma steady-state levels of racemic methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine were then measured in these individuals. The rs10403955 (T allele in intron 1), rs3745274 (G allele in exon 4), rs2279345 (T allele in intron 5), and rs707265 (A allele in exon 9) CYP2B6 allele types were found to be significantly associated with a higher clearance, a lower plasma concentration, and a lower concentration-to-dosage (C/D) ratio of (S)-methadone (P < 0.0017). Two haplotype blocks of a trinucleotide haplotype (rs8100458-rs10500282-rs10403955 in intron 1) and a hexanucleotide haplotype (rs2279342-rs3745274-rs2279343-rs2279345-rs1038376-rs707265 from intron 2 to exon 9) were constructed within CYP2B6. The major combinations of T-T-T and A-G-A-T-A-A of these particular haplotypes showed significant associations with the plasma concentrations of S-methadone and its C/D ratio (P < 0.0001, respectively). We conclude that genetic polymorphisms in the CYP2B6 gene may therefore be indicators of the clearance, plasma concentration and C/D ratio of S-methadone.
    Date: 2011-08
    Relation: Journal of Clinical Psychopharmacology. 2011 Aug;31(4):463-469.
    Link to: http://dx.doi.org/10.1097/JCP.0b013e318222b5dd
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0271-0749&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000292284600010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79960598589
    Appears in Collections:[Yu-Li Liu] Periodical Articles
    [Keh-Ming Lin(2004-2009)] Periodical Articles
    [Sheng-Chang Wang] Periodical Articles
    [Ing-Kang Ho(2006-2011)] Periodical Articles
    [Hsiao-Hui Sophie Tsou] Periodical Articles
    [Pei-Sheng Lin] Periodical Articles
    [Chin-Fu Hsiao] Periodical Articles

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