CYP2B6 Polymorphisms Influence the Plasma Concentration and Clearance of the Methadone S-Enantiomer

• DOI: 10.1097/jcp.0b013e318222b5dd
• Publication Date: 2011-06-21T06:49:40Z
• Authors: Sheng-Chang Wang; Ing-Kang Ho; Hsiao-Hui Tsou; Jia-Ni Tian; Chin-Fu Hsiao; Chia-Hui Chen; Happy Kuy-Lok Tan; Linen Lin; Chi-Shin Wu; Lien-Wen Su; Chieh-Liang Huang; Yi-Hong Yang; Ming-Lun Liu; Keh-Ming Lin; Chun-Yu Chen; Shu Chih Liu; Hsiao-Yu Wu; Hsiu-Wen Chan; Ming-Hsien Tsai; Pei-Sheng Lin; Yu-Li Liu
• Keywords: CYP2B6; Methadone maintenance

Methadone is a racemic compound composed of the R-form and S-form enantiomers. The drug usually used in maintenance therapy for heroin-addicted patients. In our previous study, we found that cytochrome P-450 (CYP) isozyme 2B6 preferentially metabolizes S-methadone enantiomer. We thus tested whether CYP2B6 gene polymorphisms had any influence on concentration or clearance methadone. Ten single nucleotide within this region were evaluated 366 patients undergoing methadone at least 3 months. plasma steady-state levels its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine then measured these individuals. rs10403955 (T allele intron 1), rs3745274 (G exon 4), rs2279345 5), rs707265 (A 9) types to be significantly associated with higher clearance, lower concentration, concentration-to-dosage (C/D) ratio (S)-methadone (P < 0.0017). Two haplotype blocks trinucleotide (rs8100458-rs10500282-rs10403955 1) hexanucleotide (rs2279342-rs3745274-rs2279343-rs2279345-rs1038376-rs707265 from 2 constructed CYP2B6. major combinations T-T-T A-G-A-T-A-A particular haplotypes showed significant associations concentrations C/D 0.0001, respectively). conclude genetic may therefore indicators S-methadone.