Pharmacogenomics of Methadone Maintenance Treatment

References

• Coller JK , ChristrupLL , SomogyiAA . Role of active metabolites in the use of opioids . Eur. J. Clin. Pharmacol.65 , 121 – 139 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Dole VP , NyswanderM . A medical treatment for diacetylmorphine (heroin) addiction: a clinical trial with methadone hydrochloride . JAMA193 , 80 – 84 ( 1965 ).
   Web of Science ®Google Scholar
• Gossop M . Treating drug misuse problems: evidence of effectiveness.National Treatment Agency for Substance Misuse, London, UK ( 2006 ).
   Google Scholar
• Darke S , MillsKL , RossJ , TeessonM . Rates and correlates of mortality amongst heroin users: findings from the Australian Treatment Outcome Study (ATOS), 2001–2009 . Drug Alcohol Depend.115 , 190 – 195 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Gibson A , DegenhardtL , MattickRP , AliRL , WhiteJ , O’BrienS . Exposure to opioid maintenance treatment reduces long-term mortality . Addiction103 , 462 – 468 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• United Nations Office on Drugs and Crime . World Drug Report 2012.United Nations Office on Drugs and Crime, Vienna, Austria ( 2012 ).
   Google Scholar
• National Institute on Drug Abuse . Drugs, brains and behaviour. The science of addiction.National Institute on Drug Abuse, MD, USA ( 2010 ).
   Google Scholar
• Garcia-Portilla MP , Bobes-BascaranMT , BascaranMT , SaizP , BobesJ.  Long-term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack? Long-term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?Br. J. Clin. Pharmacol.77 , 272 – 284 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Faggiano F , Vigna-TagliantiF , VersinoE , LemmaP . Methadone maintenance at different doasages for opioid dependence . Cochrane Database Syst. Rev.3 , CD002208 ( 2003 ).
   PubMedGoogle Scholar
• Degenhardt L , RandallD , HallW , LawM , ButlerT , BurnsL . Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: risk factors and lives saved . Drug Alcohol Depend.105 , 9 – 15 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Stallvik M , NordstrandB , KristensenØ , BathenJ , SkogvollE , SpigsetO . Corrected QT interval during treatment with methadone and buprenorphine – relation to doses and serum concentrations . Drug Alcohol Depend.129 , 88 – 93 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Martell BA , ArnstenJH , RayB , GourevitchMN . The impact of methadone induction on cardiac conduction in opiate users . Ann. Int. Med.139 , 154 – 155 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Somogyi AA , BarrattDT , CollerJK . Pharmacogenetics of opioids . Clin. Pharmacol. Ther.81 , 429 – 444 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Lötsch J , SkarkeC , LiefholdJ , GeisslingerG . Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives . Clin. Pharmacokinet.43 , 983 – 1013 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Sadhasivam S , ChidambaranV . Pharmacogenomics of opioids and perioperative pain management . Pharmacogenomics13 , 1719 – 1740 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Vuilleumier P , StamerUM , LandauR . Pharmacogenomic considerations in opioid analgesia . Pharmgenomics Pers. Med.5 , 73 – 87 ( 2012 ).
   PubMedGoogle Scholar
• Levran O , YuferovV , KreekMJ.  The genetics of the opioid system and specific drug addictions The genetics of the opioid system and specific drug addictions . Hum. Genet.131 , 823 – 842 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Bylund DB , BondRA , ElkenburgDC , HiebleJP , Hills , R , MinnemanKP , ParraS . Opioid receptors . IUPHAR/BPS Guide to pharmacology . www.guidetopharmacology.org  
   Google Scholar
• Kristensen K , ChristensenH , ChristrupLL . The mu1, mu2, delta, kappa opioid receptor profiles of methadone stereoisomers and morphine . Life Sci.56 , PL45 – PL50 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Codd EE , ShankRP , SchupskyJJ , RaffaRB . Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception . J. Pharmacol. Exp. Ther.274 , 1263 – 1270 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Ebert B , AndersenS , Krogsgaard-LarsenP . Ketobemidone, methadone and pethidine are non-competitive N-methyl-D-aspartate (NMDA) antagonists in the rat cortex and spinal cord . Neurosci. Lett.187 , 165 – 168 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Eap CB , CrettolS , RougierJSet al. Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers . Clin. Pharmacol. Ther.81 , 719 – 728 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Meresaar U , NilssonMI , HolmstrandJ , AnggardE . Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method . Eur. J. Clin. Pharmacol.20 , 473 – 478 ( 1981 ).
   PubMed Web of Science ®Google Scholar
• Foster DJ , SomogyiAA , WhiteJM , BochnerF . Population pharmacokinetics of (R)-, (S)- and rac-methadone in methadone maintenance patients . Br. J. Clin. Pharmacol.57 , 742 – 755 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Eap CB , CuendetC , BaumannP . Binding of d-methdone, l-methadone, and dl-methadone to proteins in plasma of healthy volunteers: role of the variants of alpha 1-acid glycoprotein . Clin. Pharmacol. Ther.47 , 388 – 346 ( 1990 ).
   Web of Science ®Google Scholar
• Romach MK , PiafskyKM , AbelJG , KhouwV , SellersEM . Methadone binding to orosomucoid (alpha 1-acid glycoprotein): determinant of free fraction in plasma . Clin. Pharmacol. Ther.29 , 211 – 217 ( 1981 ).
   PubMed Web of Science ®Google Scholar
• Foster DJ , SomogyiAA , DyerKR , WhiteJM , BochnerF . Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients . Br. J. Clin. Pharmacol.50 , 427 – 440 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Morton EB . The clinical pharmacology of methadone induction . PhD thesis, University of Adelaide, Adelaide ( 2007 ). //////http://digital.library.adelaide.edu.au/dspace/handle/2440/41434
   Google Scholar
• Eap CB , BourquinM , MartinJet al. Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment . Drug Alcohol Depend.61 , 47 – 54 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Dorsey JS . Serum methadone levels and optimal dosing in methadone maintained patients. Presented at: American Association for the Treatment of Opioid Dependence Conference.Washington, DC, USA , 13–16 April 2003.  
   Google Scholar
• Okruhlica L , ValentovaJ , DevinskyF , FormakovaS , KlempovaD . Methadone serum concentration and its relationship to methadone dose revisited . Heroin Add. Rel. Clin. Probl.7 , 49 – 58 ( 2005 ).
   Google Scholar
• Isbell H , EisenmanAJ.  The addiction liability of some drugs of the methadon series The addiction liability of some drugs of the methadon series . J. Pharmacol. Exp. Ther.93 , 305 – 313 ( 1948 ).
   PubMed Web of Science ®Google Scholar
• White JM , IrvineRJ.  Mechanisms of fatal opioid overdose Mechanisms of fatal opioid overdose . Addiction94 , 961 – 972 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• NCBI OPRM1 variation viewer . //=www.ncbi.nlm.nih.gov/sites/varvu?gene=4988
   Google Scholar
• Lötsch J , GeisslingerG . Are mu-opioid receptor polymorphisms important for clinical opioid therapy?Trends Mol. Med.11 , 82 – 89 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Huang P , ChenC , MagueSD , BlendyJA , Liu-ChenLY . A common single nucleotide polymorphism A118G of the mu opioid receptor alters its N-glycosylation and protein stability . Biochem. J.441 , 379 – 386 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Zhang Y , WangD , JohnsonAD , PappAC , SadeeW . Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G . J. Biol. Chem.280 , 32618 – 32624 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Bond C , LaForgeKS , TianMet al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction . Proc. Natl Acad. Sci. USA95 , 9608 – 9613 ( 1998 ).
   PubMed Web of Science ®Google Scholar
• Mura E , GovoniS , RacchiMet al. Consequences of the 118A>G polymorphism in the OPRM1 gene: translation from bench to bedside? J. Pain Res. 6 , 331 – 353 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lötsch J , SkarkeC , WietingJet al. Modulation of the central nervous effects of levomethadone by genetic polymorphisms potentially affecting its metabolism, distribution, and drug action . Clin. Pharmacol. Ther.79 , 72 – 89 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Crettol S , BessonJ , Croquette-KrokarMet al. Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment . Prog. Neuro-Psychopharmacol. Biol. Psych.32 , 1722 – 1727 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Barratt DT , CollerJK , HallinanRet al. ABCB1 haplotype and OPRM1 118A>G genotype interaction in methadone maintenance treatment pharmacogenetics . Pharmgenomics Pers. Med.5 , 53 – 62 ( 2012 ).
   PubMedGoogle Scholar
• Hung CC , ChiouMH , HuangBHet al. Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients . Pharmacogenomics12 , 1525 – 1533 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Campa D , GioiaA , TomeiA , PoliP , BaraleR . Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief . Clin. Pharmacol. Ther.83 , 559 – 566 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Fonseca F , GratacosM , EscaramisGet al. Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes . Mol. Diagn. Ther.14 , 171 – 178 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Wang SC , TsouHH , ChenCHet al. Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients . Eur. Neuropsychopharmacol.22 , 695 – 703 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Wachman EM , HayesMJ , BrownMSet al. Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome . JAMA309 , 1821 – 1827 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Iribarne C , BerthouF , BairdSet al. Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes . Chem. Res. Toxicol.9 , 365 – 373 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Foster DJ , SomogyiAA , BochnerF . Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4 . Br. J. Clin. Pharmacol.47 , 403 – 412 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Wang J-S , DeVaneCL . Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro . Drug Metab. Dispos.31 , 742 – 747 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Kharasch ED , HofferC , WhittingtonD , SheffelsP . Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition and miotic effects of methadone . Clin. Pharmacol. Ther.76 , 250 – 269 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Gerber JG , RhodesRJ , GalJ.  Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19 Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19 . Chirality16 , 36 – 44 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Coller JK , JoergensenC , FosterDJRet al. Lack of influence of CYP2D6 genotype on the clearance of (R)-, (S)- and racemic-methadone . Int. J. Clin. Pharmacol. Ther.45 , 410 – 417 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Sim S , Ingelman-SundbergM , DalyAK , NebertDW . Home page of the human cytochrome P450 (CYP) allele nomenclature database . www.cypalleles.ki.se  
   Google Scholar
• Guan S , HuangM , LiXF , ChenX , ChanE , ZhouS-F . Intra- and inter-ethnic differences in the allele frequencies of cytochrome P450 2B6 gene in Chinese . Pharm. Res.23 , 1983 – 1990 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Zanger UM , KleinK . Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance . Front. Genet.4 , 24 ( 2013 ).
   PubMedGoogle Scholar
• Daly AK . Pharmacogenetics of the cytochromes P450 . Curr. Top. Med. Chem.4 , 1733 – 1744 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Zanger UM , RaimundoS , EichelbaumM . Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry . Naunyn-Schmiedeberg’s Arch. Pharmacol.369 , 23 – 37 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Teh LK , BertilssonL . Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance . Drug Metab. Pharmacokin.27 , 55 – 67 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Lovlie R , DalyAK , MatreGE , MolvenA , SteenVM . Polymorphisms in CYP2D6 duplication-negative individuals with the ultrarapid metabolizer phenotype: a role for the CYP2D6*35 allele in ultrarapid metabolism?Pharmacogenetics11 , 45 – 55 ( 2001 ).
   PubMedGoogle Scholar
• Gadel S , CraffordA , ReginaK , KharaschED . Methadone N-demethylation by the common CYP2B6 allelic variant CYP2B6.6 . Drug Metab. Dispos.41 , 709 – 713 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Crettol S , DeglonJ-J , BessonJet al. Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment . Clin. Pharmacol. Ther.78 , 593 – 604 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Crettol S , DeglonJJ , BessonJet al. ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment . Clin. Pharmacol. Ther.80 , 668 – 681 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Dobrinas M , CrettolS , OnedaBet al. Contribution of CYP2B6 alleles in explaining extreme (S)-methadone plasma levels: A CYP2B6 gene resequencing study . Pharmacogenet. Genomics23 , 84 – 93 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Wang SC , HoIK , TsouHHet al. CYP2B6 polymorphisms influence the plasma concentration and clearance of the methadone S-enantiomer . J. Clin. Psychopharmacol.31 , 463 – 469 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Bunten H , LiangWJ , PounderD , SeneviratneC , OsseltonMD . CYP2B6 and OPRM1 gene variations predict methadone-related deaths . Addict. Biol.16 , 142 – 144 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Tsai HJ , WangSC , TianJNet al. PXR polymorphisms interacted with CYP2B6 polymorphisms on methadone metabolites . J. Clin. Psychopharmacol.33 , 137 – 140 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Eap CB , BrolyF , MinoAet al. Cytochrome P450 2D6 genotype and methadone steady-state concentrations . J. Clin. Psychopharmacol.21 , 229 – 234 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Crettol S , DeglonJ-J , BessonJet al. ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment . Clin. Pharmacol. Ther80 , 668 – 681 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Chen CH , WangSC , TsouHHet al. Genetic polymorphisms in CYP3A4 are associated with withdrawal symptoms and adverse reactions in methadone maintenance patients . Pharmacogenomics12 , 1397 – 1406 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Fonseca F , De La TorreR , DiazLet al. Conribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response . PLoS ONE6 , e19527 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Levran O , PelesE , HamonS , RandesiM , AdelsonM , KreekMJ.  CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction . Addict. Biol.18 , 709 – 716 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• De Fazio S , GallelliL , De SienaA , De SarroG , ScordoMG . Role of CYP3A5 in abnormal clearance of methadone . Ann. Pharmacother.42 , 893 – 897 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Crettol S , DigonP , GolayKP , BrawandM , EapCB . In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites . Pharmacology80 , 304 – 311 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Hassan HE , MyersAL , CoopA , EddingtonND . Differential involvement of P-glycoprotein (ABCB1) in permeability, tissue distribution, and antinociceptive activity of methadone, buprenorphine, and diprenorphine: in vitro and in vivo evaluation . J. Pharm. Sci.98 , 4928 – 4940 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Tournier N , ChevillardL , MegarbaneB , PirnayS , ScherrmannJM , DeclevesX . Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) . Int. J. Neuropsychopharmacol.13 , 905 – 915 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Hung CC , ChiouMH , TengYN , HsiehYW , HuangCL , LaneHY . Functional impact of ABCB1 variants on interactions between P-glycoprotein and methadone . PLoS ONE8 , e59419 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Zhou SF . Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition . Xenobiotica38 , 802 – 832 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Wang J-S , RuanY , TaylorRM , DonovanJL , MarkowitzJS , DeVaneCL . Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P-glycoprotein deficiency in the blood–brain barrier of Abcb1a gene knockout mice . Psychopharmacology173 , 132 – 138 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Ortega I , RodriguezM , SuarezE , Perez-RuixoJJ , CalvoR . Modeling methadone pharmacokinetics in rats in presence of P-glycoprotein inhibitor valspodar . Pharm. Res.24 , 1299 – 1308 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Kharasch ED , HofferC , WhittingtonD . The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone . Br. J. Clin. Pharmacol.57 , 600 – 610 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Kharasch ED , HofferC , WhittingtonD , WalkerA , BedynekPS . Methadone pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and gastrointestinal drug transport . Anesthesiology110 , 660 – 672 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Bendayan R , RonaldsonPT , GingrasD , BendayanM . In situ localization of P-glycoprotein (ABCB1) in human and rat brain . J. Histochem. Cytochem.54 , 1159 – 1167 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Chan GN , SaldiviaV , YangY , PangH , de LannoyI , BendayanR . In vivo induction of P-glycoprotein expression at the mouse blood–brain barrier: an intracerebral microdialysis study . J. Neurochem.127 ( 3 ), 342 – 352 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lin JH , YamazakiM . Clinical relevance of P-glycoprotein in drug therapy . Drug Metab. Rev.35 , 417 – 454 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Dagenais C , GraffCL , PollackGM . Variable modulation of opioid brain uptake by P-glycoprotein in mice . Biochem. Pharmacol.67 , 269 – 276 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Thompson SJ , KoszdinK , BernardsCM . Opiate-induced analgesia is increased and prolonged in mice lacking P-glycoprotein . Anesthesiology92 , 1392 – 1399 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Kharasch ED , WalkerA , WhittingtonD , HofferC , BedynekPS . Methadone metabolism and clearance are induced by nelfinavir despite inhibition of cytochrome P4503A (CYP3A) activity . Drug Alcohol Depend.101 , 158 – 168 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Kreek MJ , GarfieldJW , GutjahrCL , GiustiLM . Rifampin-induced methadone withdrawal . N. Engl. J. Med.294 , 1104 – 1106 ( 1976 ).
   PubMed Web of Science ®Google Scholar
• Eich-Hochli D , OppligerR , GolayKP , BaumannP , EapCB . Methadone maintenance treatment and St. John’s Wort – a case report . Pharmacopsychiatry36 , 35 – 37 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Ieiri I . Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) . Drug Metab. Pharmacokin.27 , 85 – 105 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Wolf SJ , BachtiarM , WangJ , SimTS , ChongSS , LeeCG . An update on ABCB1 pharmacogenetics: insights from a 3D model into the location and evolutionary conservation of residues corresponding to SNPs associated with drug pharmacokinetics . Pharmacogenomics J.11 , 315 – 325 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Kimchi-Sarfaty C , GribarJJ , GottesmanMM . Functional characterization of coding polymorphisms in the human MDR1 gene using a vaccinia virus expression system . Mol. Pharmacol.62 , 1 – 6 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Salama NN , YangZ , BuiT , HoRJY . MDR1 haplotypes significantly minimize intracellular uptake and transcellular P-gp substrate transport in recombinant LLC-PK1 cells . J. Pharm. Sci.95 , 2293 – 2308 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Aird RE , ThomsonM , MacphersonJS , ThurstonDE , JodrellDI , GuichardSM . ABCB1 genetic polymorphism influences the pharmacology of the new pyrrolobenzodiazepine derivative SJG-136 . Pharmacogenomics J.8 , 289 – 296 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Gow JM , HodgesLM , ChinnLW , KroetzDL . Substrate-dependent effects of human ABCB1 coding polymorphisms . J. Pharmacol. Exp. Ther.325 , 435 – 442 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Kimchi-Sarfaty C , OhJM , KimIWet al. A silent polymorphism in the MDR1 gene changes substrate specificity . Science315 , 525 – 528 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Coller JK , BarrattDT , DahlenK , LoennechenMH , SomogyiAA . ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals . Clin. Pharmacol. Ther.80 , 682 – 690 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Crettol S , DeglonJ-J , BessonJet al. No influence of ABCB1 haplotypes on methadone dosage requirement . Clin. Pharmacol. Ther.83 , 668 – 669 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Uehlinger C , CrettolS , ChassotPet al. Increased (R)-methadone plasma concentrations by quetiapine in cytochrome P450s and ABCB1 genotyped patients . J. Clin. Psychopharmacol.27 , 273 – 278 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Levran O , O’HaraK , PelesEet al. ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence . Hum. Mol. Genet.17 , 2219 – 2227 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Tian JN , HoIK , TsouHHet al. UGT2B7 genetic polymorphisms are associated with the withdrawal symptoms in methadone maintenance patients . Pharmacogenomics13 , 879 – 888 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Oneda B , CrettolS , BochudMet al. beta-Arrestin2 influences the response to methadone in opioid-dependent patients . Pharmacogenomics J.11 , 258 – 266 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Lotsch J , PrussH , VehRW , DoehringA . A KCNJ6 (Kir3.2, GIRK2) gene polymorphism modulates opioid effects on analgesia and addiction but not on pupil size . Pharmacogenet. Genomics20 , 291 – 297 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• de Cid R , FonsecaF , GratacosMet al. BDNF variability in opioid addicts and response to methadone treatment: preliminary findings . Genes Brain Behav.7 , 515 – 522 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Levran O , PelesE , HamonSet al. Nerve growth factor beta polypeptide (NGFB) genetic variability: association with the methadone dose required for effective maintenance treatment . Pharmacogenomics J.12 , 319 – 327 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Doehring A , HentigN , GraffJet al. Genetic variants altering dopamine D2 receptor expression or function modulate the risk of opiate addiction and the dosage requirements of methadone substitution . Pharmacogenet. Genomics19 , 407 – 414 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Morrish GA , FosterDJ , SomogyiAA . Differential in vitro inhibition of M3G and M6G formation from morphine by (R)- and (S)-methadone and structurally related opioids . Br. J. Clin. Pharmacol.61 , 326 – 335 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Gelston EA , CollerJK , LopatkoOVet al. Methadone inhibits CYP2D6 and UGT2B7/2B4in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects . Br. J. Clin. Pharmacol.73 , 786 – 794 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Nishizawa D , NagashimaM , KatohRet al. Association between KCNJ6 (GIRK2) gene polymorphisms and postoperative analgesic requirements after major abdominal surgery . PLoS ONE4 , e7060 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Cheng CY , HongCJ , YuYW , ChenTJ , WuHC , TsaiSJ.  Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males . Brain Res. Mol. Brain Res.140 , 86 – 90 ( 2005 ).
   PubMedGoogle Scholar
• Lawford BR , YoungRM , NobleEPet al. The D2 dopamine receptor A1 allele and opioid dependence: association with heroin use and response to methadone treatment . Am. J. Med. Genet.96 , 592 – 598 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Barratt DT , CollerJK , SomogyiAA . Association between the DRD2 A1 allele and response to methadone and buprenorphine maintenance treatments . Am. J. Med. Genet. B Neuropsychiatr. Genet.141B , 323 – 331 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Levran O , PelesE , RandesiMet al. Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction . Pharmacogenomics14 , 755 – 768 ( 2013 ).
   PubMed Web of Science ®Google Scholar