Interindividual variability of methadone response: Impact of genetic polymorphism

Molecular Diagnosis and Therapy

Volumn 12, Issue 2, 2008, Pages 109-124

  Li, Yongfang ^a,b   Kantelip, Jean Pierre ^a   Gerritsen Van Schieveen, Pauline ^a   Davani, Siamak ^a  

^a UNIVERSITY HOSPITAL OF BESANÇON   (France)

^b QINGHAI UNIVERSITY   (China)

Author keywords

Dose prediction; Drug interactions; Genetic polymorphism; Methadone, therapeutic use; Pharmacogenetics

Indexed keywords

2 ETHYLIDENE 1,5 DIMETHYL 3,3 DIPHENYLPYRROLIDINE; ALPRAZOLAM; ALPRENOLOL; AMFEBUTAMONE; AMIODARONE; AMITRIPTYLINE; AMLODIPINE; AMPHETAMINE DERIVATIVE; ANTICONVULSIVE AGENT; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ANTIRETROVIRUS AGENT; ATENOLOL; BARBITURIC ACID DERIVATIVE; CHLORPROMAZINE; CIMETIDINE; CINNARIZINE; CIPROFLOXACIN; CLOMIPRAMINE; CYTOCHROME P450; EFAVIRENZ; GLYCOPROTEIN P; METHADONE; MORPHINE; MU OPIATE RECEPTOR; MULTIDRUG RESISTANCE PROTEIN 1; OPIATE ANTAGONIST; PSYCHOTROPIC AGENT; TUBERCULOSTATIC AGENT; UNINDEXED DRUG;

AREA UNDER THE CURVE; BILE DUCT PRESSURE; CANCER PAIN; CHRONIC PAIN; CONSTIPATION; DIZZINESS; DRUG ANTAGONISM; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE TITRATION; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; DRUG METABOLISM; DRUG MONITORING; DRUG OVERDOSE; DRUG PROTEIN BINDING; DRUG RESEARCH; DRUG TOLERANCE; DRUG URINE LEVEL; DYSPHORIA; ENZYME ACTIVITY; ETHNIC DIFFERENCE; EUPHORIA; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HUMAN; HYPOTENSION; LONG QT SYNDROME; LOW DRUG DOSE; MENTAL CLOUDING; MENTAL DISEASE; MIOSIS; NAUSEA; NEUROPATHIC PAIN; NONHUMAN; OPIATE ADDICTION; PRIORITY JOURNAL; PRURITUS; QT PROLONGATION; RESPIRATION DEPRESSION; REVIEW; SEDATION; SIDE EFFECT; TORSADE DES POINTES; UNSPECIFIED SIDE EFFECT; URINE RETENTION; VOMITING;

EID: 42449123284     PISSN: 11771062     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF03256276     Document Type: Review

References (160)

1. Bertschy G. Methadone maintenance treatment: an update. Eur Arch Psychiatry Clin Neurosci 1995; 245 (2): 114-24
2. Farrell M, Ward J, Mattick R, et al. Methadone maintenance treatment in opiate dependence: a review. BMJ 1994 Oct 15; 309 (6960): 997-1001
3. Connor PD, Sampson PD, Bookstein FL, et al. Direct and indirect effects of prenatal alcohol damage on executive function. Dev Neuropsychol 2000; 18 (3): 331-54
4. Conversation with Vincent Dole. Addiction 1994; 89 (1): 23-9
5. Olsen GD. Methadone binding to human plasma proteins. Clin Pharmacol Ther 1973 May-Jun; 14 (3): 338-43
6. Austrialian Government, National Drug Strategy. Clinical guidelines and procedures for the use of methadone in the maintenance treatment of opioid dependence [online]. Available from URL: http://www.health.vic.gov.au/dpu/ downloads/guidelines-methadone.pdf [Accessed 2008 Mar 25]
7. Gourlay GK, Cherry DA, Cousins MJ. A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Pain 1986 Jun; 25 (3): 297-312
8. Manfredi PL, Borsook D, Chandler SW, et al. Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations. Pain 1997 Mar; 70 (1): 99-101
9. Ripamonti C, Zecca E, Bruera E. An update on the clinical use of methadone for cancer pain. Pain 1997 Apr; 70 (2-3): 109-15
10. Bruera E, Pereira J, Watanabe S, et al. Opioid rotation in patients with cancer pain: a retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer 1996 Aug 15; 78 (4): 852-7
11. Mitchell TB, Dyer KR, Newcombe D, et al. Subjective and physiological responses among racemic-methadone maintenance patients in relation to relative (S)- vs. (R)-methadone exposure. Br J Clin Pharmacol 2004; 58 (6): 609-17
12. Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet 2002; 41 (14): 1153-93
13. Garrido MJ, Troconiz IF. Methadone: a review of its pharmacokinetic/ pharmacodynamic properties. J Pharmacol Toxicol Methods 1999 Oct; 42 (2): 61-6
14. Inturrisi CE, Verebely K. Disposition of methadone in man after a single oral dose. Clin Pharmacol Ther 1972 Nov-Dec;13 (6): 923-30
15. Oda Y, Kharasch ED. Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation. J Pharmacol Exp Ther 2001 Sep 1; 298 (3): 1021-32
16. Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain 2002 Jul-Aug; 18 (4 Suppl.): S3-13
17. Meresaar U, Nilsson MI, Holmstrand J, et al. Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method. Eur Clin Pharmacol 1981; 20 (6): 473-8
18. Boulton DW, Arnaud P, DeVane CL. Pharmacokinetics and pharmacodynamics of methadone enantiomers after a single oral dose of racemate. Clin Pharmacol Ther 2001 Jul; 70 (1): 48-57
19. Nilsson MI, Anggard E, Holmstrand J, et al. Pharmacokinetics of methadone during maintenance treatment: adaptive changes during the induction phase. Eur J Clin Pharmacol 1982; 22 (4): 343-9
20. Moody DE, Alburges ME, Parker RJ, et al. The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone. Drug Metab Dispos 1997 Dec; 25 (12): 1347-53
21. Vaupel DB, Jasinski DR. l-Alpha-acetylmethadol, l-alpha-acetyl-N- normethadol and l-alpha-acetyl-N,N-dinormethadol: comparisons with morphine and methadone in suppression of the opioid withdrawal syndrome in the dog. J Pharmacol Exp Ther 1997 Nov 1; 283 (2): 833-42
22. Anggard E, Gunne LM, Homstrand J, et al. Disposition of methadone in methadone maintenance. Clin Pharmacol Ther 1975 Mar; 17 (3): 258-66
23. Kreek MJ, Bencsath FA, Field FH. Effects of liver disease on urinary excretion of methadone and metabolites in maintenance patients: quantitation by direct probe chemical ionization mass spectrometry. Biomed Mass Spectrom 1980 Sep; 7 (9): 385-95
24. Kreek MJ, Bencsath FA, Fanizza A, et al. Effects of liver disease on fecal excretion of methadone and its unconjugated metabolites in maintenance patients: quantitation by direct probe chemical ionization mass spectrometry. Biomed Mass Spectrom 1983 Oct; 10 (10): 544-9
25. Furlan V, Hafi A, Dessalles M, et al. Methadone is poorly removed by haemodialysis. Nephrol Dial Transplant 1999 Jan 1; 14 (1): 254-5
26. Reisine T, Law SF, Blake A, et al. Molecular mechanisms of opiate receptor coupling to G proteins and effector systems. Ann N Y Acad Sci 1996 Mar 22; 780: 168-75
27. Ehret GB, Voide C, Gex-Fabry M, et al. Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors. Arch Intern Med 2006 Jun 26; 166 (12): 1280-7
28. Iskandar SB, Abi-Saleh BS, Mechleb BK, et al. Methadone and torsade de pointes: case report and review of the literature. Tenn Med 2007 Feb; 100 (2): 35-7, 42
29. Nilsson MI, Meresaar U, Anggard E. Clinical pharmacokinetics of methadone. Acta Anaesthesiol Scand Suppl 1982; 74: 66-9
30. Rebbeck TR, Jaffe JM, Walker AH, et al. Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 1998 Aug 19; 90 (16): 1225-9
31. Gerber JG, Rhodes RJ, Gal J. Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19. Chirality 2004 Jan; 16 (1): 36-44
32. Wang JS, DeVane CL. Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro. Drug Metab Dispos 2003 Jun; 31 (6): 742-7
33. Begre S, von Bardeleben U, Ladewig D, et al. Paroxetine increases steady-state concentrations of (R)-methadone in CYP2D6 extensive but not poor metabolizers. J Clin Psychopharmacol 2002 Apr; 22 (2): 211-5
34. Eap CB, Broly F, Mino A, et al. Cytochrome P450 2D6 genotype and methadone steady-state concentrations. J Clin Psychopharmacol 2001 Apr; 21 (2): 229-34
35. Crettol S, Deglon JJ, Besson J, et al. Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment. Clin Pharmacol Ther 2005 Dec; 78 (6): 593-604
36. Foster DJ, Somogyi AA, Bochner F. Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4. Br J Clin Pharmacol 1999 Apr; 47 (4): 403-12
37. Iribarne C, Berthou F, Baird S, et al. Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol 1996; 9 (2): 365-73
38. Shinderman M, Maxwell S, Brawand-Amey M, et al. Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses. Drug Alcohol Depend 2003 Mar 1; 69 (2): 205-11
39. Kharasch ED, Hoffer C, Whittington D, et al. Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther 2004 Sep; 76 (3): 250-69
40. Shimada T, Yamazaki H, Mimura M, et al. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994 Jul; 270 (1): 414-23
41. Westlind A, Lofberg L, Tindberg N, et al. Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5′-upstream regulatory region. Biochem Biophys Res Commun 1999 May 27; 259 (1): 201-5
42. Wojnowski L. Genetics of the variable expression of CYP3A in humans. Ther Drug Monit 2004 Apr; 26 (2): 192-9
43. Eiselt R, Domanski TL, Zibat A, et al. Identification and functional characterization of eight CYP3A4 protein variants. Pharmacogenetics 2001 Jul; 11 (5): 447-58
44. van Schaik RH. Cancer treatment and pharmacogenetics of cytochrome P450 enzymes. Invest New Drugs 2005 Dec; 23 (6): 513-22
45. Tayeb MT, Clark C, Sharp L, et al. CYP3A4 promoter variant is associated with prostate cancer risk in men with benign prostate hyperplasia. Oncol Rep 2002 May-Jun; 9 (3): 653-5
46. Lamba JK, Lin YS, Thummel K, et al. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics 2002 Mar; 12 (2): 121-32
47. Walker AH, Jaffe JM, Gunasegaram S, et al. Characterization of an allelic variant in the nifedipine-specific element of CYP3A4: ethnic distribution and implications for prostate cancer risk. Mutations in brief no. 191. Hum Mutat 1998; 12 (4): 289
48. Amirimani B, Walker AH, Weber BL, et al. Response RE: modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 1999 Sep 15; 91 (18): 1588-90
49. Spurdle AB, Goodwin B, Hodgson E, et al. The CYP3A4*1B polymorphism has no functional significance and is not associated with risk of breast or ovarian cancer. Pharmacogenetics 2002 Jul; 12 (5): 355-66
50. Crettol S, Deglon JJ, Besson J, et al. ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment. Clin Pharmacol Ther 2006 Dec; 80 (6): 668-81
51. Sata F, Sapone A, Elizondo G, et al. CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity. Clin Pharmacol Ther 2000 Jan; 67 (1): 48-56
52. Dai D, Tang J, Rose R, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 2001 Dec; 299 (3): 825-31
53. Hsieh KP, Lin YY, Cheng CL, et al. Novel mutations of CYP3A4 in Chinese. Drug Metab Dispos 2001 Mar; 29 (3): 268-73
54. Kharasch ED, Hoffer C, Whittington D. 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 2004 May; 57 (5): 600-10
55. Totah RA, Allen KE, Sheffels P, et al. Enantiomeric metabolic interactions and stereoselective human methadone metabolism. J Pharmacol Exp Ther 2007 Apr 1; 321 (1): 389-99
56. Lang T, Klein K, Fischer J, et al. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 2001 Jul; 11 (5): 399-415
57. Ariyoshi N, Sawamura Y, Kamataki T. A novel single nucleotide polymorphism altering stability and activity of CYP2a6. Biochem Biophys Res Commun 2001 Mar 2; 281 (3): 810-4
58. Jinno H, Tanaka-Kagawa T, Ohno A, et al. Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab Dispos 2003 Apr; 31 (4): 398-403
59. Lamba V, Lamba J, Yasuda K, et al. Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther 2003 Dec; 307 (3): 906-22
60. Xie HJ, Yasar U, Lundgren S, et al. Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation. Pharmacogenomics J 2003; 3 (1): 53-61
61. Hiratsuka M, Takekuma Y, Endo N, et al. Allele and genotype frequencies of CYP2B6 and CYP3A5 in the Japanese population. Eur J Clin Pharmacol 2002 Sep; 58 (6): 417-21
62. Tsuchiya K, Gatanaga H, Tachikawa N, et al. Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem Biophys Res Commun 2004 Jul 9; 319 (4): 1322-6
63. Kirchheiner J, Klein C, Meineke I, et al. Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics 2003 Oct; 13 (10): 619-26
64. Eap CB, Crettol S, Rougier JS, et al. Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin Pharmacol Ther 2007 May; 81 (5): 719-28
65. Eap CB, Bertschy G, Powell K, et al. Fluvoxamine and fluoxetine do not interact in the same way with the metabolism of the enantiomers of methadone. J Clin Psychopharmacol 1997 Apr; 17 (2): 113-7
66. Sim SC, Ingelman-Sundberg M. The human cytochrome P450 allele nomenclature committee website: submission criteria, procedures, and objectives. Methods Mol Biol 2006; 320: 183-91
67. Somogyi AA, Barratt DT, Coller JK. Pharmacogenetics of opioids. Clin Pharmacol Ther 2007 Mar; 81 (3): 429-44
68. Nakamura K, Goto F, Ray WA, et al. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther 1985 Oct; 38 (4): 402-8
69. Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2002 Mar; 3 (2): 229-43
70. Lotsch J, Skarke C, Wieting J, et al. Modulation of the central nervous effects of levomethadone by genetic polymorphisms potentially affecting its metabolism, distribution, and drug action. Clin Pharmacol Ther 2006 Jan; 79 (1): 72-89
71. Perez de Los Cobos J, Sinol N, Trujols J, et al. Association of CYP2D6 ultrarapid metabolizer genotype with deficient patient satisfaction regarding methadone maintenance treatment. Drug Alcohol Depend 2007 Jul 10; 89 (2-3): 190-4
72. Shiran MR, Chowdry J, Rostami-Hodjegan A, et al. A discordance between cytochrome P450 2D6 genotype and phenotype in patients undergoing methadone maintenance treatment. Br J Clin Pharmacol 2003 Aug; 56 (2): 220-4
73. Schweikl H, Taylor JA, Kitareewan S, et al. Expression of CYP1A1 and CYP1A2 genes in human liver. Pharmacogenetics 1993 Oct; 3 (5): 239-49
74. Ingelman-Sundberg M, Oscarson M, McLellan RA. Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment. Trends Pharmacol Sci 1999 Aug; 20 (8): 342-9
75. Ieiri I, Tainaka H, Morita T, et al. Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. Ther Drug Monit 2000 Jun; 22 (3): 237-44
76. Stubbins MJ, Harries LW, Smith G, et al. Genetic analysis of the human cytochrome P450 CYP2C9 locus. Pharmacogenetics 1996 Oct; 6 (5): 429-39
77. Sullivan-Klose TH, Ghanayem BI, Bell DA, et al. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996 Aug; 6 (4): 341-9
78. Kirchheiner J, Roots I, Goldammer M, et al. Effect of genetic polymorphisms in cytochrome p450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs: clinical relevance. Clin Pharmacokinet 2005; 44 (12): 1209-25
79. De Morais SM, Wilkinson GR, Blaisdell J, et al. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol 1994 Oct; 46 (4): 594-8
80. de Morais SM, Wilkinson GR, Blaisdell J, et al. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 1994 Jun 3; 269 (22): 15419-22
81. Xie HG, Stein CM, Kim RB, et al. Allelic, genotypic and phenotypic distributions of S-mephenytoin 4′-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world. Pharmacogenetics 1999 Oct; 9 (5): 539-49
82. Bouer R, Barthe L, Philibert C, et al. The roles of P-glycoprotein and intracellular metabolism in the intestinal absorption of methadone: in vitro studies using the rat everted intestinal sac. Fundam Clin Pharmacol 1999; 13 (4): 494-500
83. Nanovskaya T, Nekhayeva I, Karunaratne N, et al. Role of P-glycoprotein in transplacental transfer of methadone. Biochem Pharmacol 2005 Jun 15; 69 (12): 1869-78
84. Wang JS, Ruan Y, Taylor RM, et al. 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. Psychopharmacology (Berl) 2004 Apr; 173 (1-2): 132-8
85. Marzolini C, Paus E, Buclin T, et al. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther 2004 Jan; 75 (1): 13-33
86. Dietrich CG, Geier A, Oude Elferink RP. ABC of oral bioavailability: transporters as gatekeepers in the gut. Gut 2003 Dec; 52 (12): 1788-95
87. Chan LM, Lowes S, Hirst BH. The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 2004 Jan; 21 (1): 25-51
88. Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution. Eur J Pharm Sci 2006 Apr; 27 (5): 425-46
89. Takano M, Yumoto R, Murakami T. Expression and function of efflux drug transporters in the intestine. Pharmacol Ther 2006 Jan; 109 (1-2): 137-61
90. Thompson SJ, Koszdin K, Bernards CM. Opiate-induced analgesia is increased and prolonged in mice lacking P-glycoprotein. Anesthesiology 2000 May; 92 (5): 1392-9
91. Owen A, Goldring C, Morgan P, et al. Relationship between the C3435T and G2677T(A) polymorphisms in the ABCB1 gene and P-glycoprotein expression in human liver. Br J Clin Pharmacol 2005 Mar; 59 (3): 365-70
92. Meier Y, Pauli-Magnus C, Zanger UM, et al. Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology 2006 Jul; 44 (1): 62-74
93. Thorn M, Finnstrom N, Lundgren S, et al. Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Br J Clin Pharmacol 2005 Jul; 60 (1): 54-60
94. Kerb R. Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett 2006 Mar 8; 234 (1): 4-33
95. Ameyaw MM, Regateiro F, Li T, et al. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 2001 Apr; 11 (3): 217-21
96. Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 2000 Mar 28; 97 (7): 3473-8
97. Song P, Lamba JK, Zhang L, et al. G2677T and C3435T genotype and haplotype are associated with hepatic ABCB1 (MDR1) expression. J Clin Pharmacol 2006 Mar; 46 (3): 373-9
98. Wang D, Sadee W. Searching for polymorphisms that affect gene expression and mRNA processing: example ABCB1 (MDR1). AAPS J 2006; 8 (3): E515-20
99. Kim RB, Leake BF, Choo EF, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 2001 Aug; 70 (2): 189-99
100. Coller JK, Barratt DT, Dahlen K, et al. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Clin Pharmacol Ther 2006 Dec; 80 (6): 682-90
101. Schaeffeler E, Eichelbaum M, Brinkmann U, et al. Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet 2001 Aug 4; 358 (9279): 383-4
102. Inturrisi CE, Colburn WA, Kaiko RF, et al. Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clin Pharmacol Ther 1987 Apr; 41 (4): 392-401
103. Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology 1982 Dec; 57 (6): 458-67
104. Gourlay GK, Willis RJ, Wilson PR. Postoperative pain control with methadone: influence of supplementary methadone doses and blood concentration-response relationships. Anesthesiology 1984 Jul; 61 (1): 19-26
105. Inturrisi CE, Portenoy RK, Max MB, et al. Pharmacokinetic-pharmacodynamic relationships of methadone infusions in patients with cancer pain. Clin Pharmacol Ther 1990 May; 47 (5): 565-77
106. Hiltunen AJ, Beck O, Hjemdahl P, et al. Rated well-being in relation to plasma concentrations of l- and d-methadone in satisfied and dissatisfied patients on methadone maintenance treatment. Psychopharmacology (Berl) 1999 Apr; 143 (4): 385-93
107. Dyer KR, Foster DJ, White JM, et al. Steady-state pharmacokinetics and pharmacodynamics in methadone maintenance patients: comparison of those who do and do not experience withdrawal and concentration-effect relationships. Clin Pharmacol Ther 1999 Jun; 65 (6): 685-94
108. Dyer KR, White JM, Foster DJ, et al. The relationship between mood state and plasma methadone concentration in maintenance patients. J Clin Psychopharmacol 2001 Feb; 21 (1): 78-84
109. Ikeda K, Ide S, Han W, et al. How individual sensitivity to opiates can be predicted by gene analyses. Trends Pharmacol Sci 2005 Jun; 26 (6): 311-7
110. Lotsch J, Geisslinger G. Are mu-opioid receptor polymorphisms important for clinical opioid therapy? Trends Mol Med 2005 Feb; 11 (2): 82-9
111. Bond C, LaForge KS, Tian M, et 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 U S A 1998 Aug 4; 95 (16): 9608-13
112. Beyer A, Koch T, Schroder H, et al. Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor. J Neurochem 2004 May; 89 (3): 553-60
113. Befort K, Filliol D, Decaillot FM, et al. A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling. J Biol Chem 2001 Feb 2; 276 (5): 3130-7
114. Zhang Y, Wang D, Johnson AD, et al. Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 2005 Sep 23; 280 (38): 32618-24
115. Lotsch J, Skarke C, Grosch S, et al. The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics 2002 Jan; 12 (1): 3-9
116. Romberg RR, Olofsen E, Bijl H, et al. Polymorphism of mu-opioid receptor gene (OPRM1:c.118A>G) does not protect against opioid-induced respiratory depression despite reduced analgesic response. Anesthesiology 2005 Mar; 102 (3): 522-30
117. Skarke C, Darimont J, Schmidt H, et al. Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers. Clin Pharmacol Ther 2003 Jan; 73 (1): 107-21
118. Oertel BG, Schmidt R, Schneider A, et al. The mu-opioid receptor gene polymorphism 118A>G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet Genomics 2006 Sep; 16 (9): 625-36
119. Klepstad P, Rakvag TT, Kaasa S, et al. The 118 A>G polymorphism in the human micro-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand 2004 Nov; 48 (10): 1232-9
120. Lotsch J, Zimmermann M, Darimont J, et al. Does the A118G polymorphism at the mu-opioid receptor gene protect against morphine-6-glucuronide toxicity? Anesthesiology 2002 Oct; 97 (4): 814-9
121. Koch T, Kroslak T, Averbeck M, et al. Allelic variation S268P of the human mu-opioid receptor affects both desensitization and G protein coupling. Mol Pharmacol 2000 Aug; 58 (2): 328-34
122. Wang D, Raehal KM, Bilsky EJ, et al. Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence. J Neurochem 2001 Jun; 77 (6): 1590-600
123. Gorman AL, Elliott KJ, Inturrisi CE. The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci Lett 1997 Feb 14; 223 (1): 5-8
124. Bulka A, Wiesenfeld-Hallin Z, Xu XJ. Differential antinociception by morphine and methadone in two sub-strains of Sprague-Dawley rats and its potentiation by dextromethorphan. Brain Res 2002 Jun 28; 942 (1-2): 95-100
125. Shimoyama N, Shimoyama M, Elliott KJ, et al. d-Methadone is antinociceptive in the rat formalin test. J Pharmacol Exp Ther 1997 Nov; 283 (2): 648-52
126. Williams NM, Bowen T, Spurlock G, et al. Determination of the genomic structure and mutation screening in schizophrenic individuals for five subunits of the N-methyl-D-aspartate glutamate receptor. Mol Psychiatry 2002; 7 (5): 508-14
127. Ohtsuki T, Sakurai K, Dou H, et al. Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia. Mol Psychiatry 2001 Mar; 6 (2): 211-6
128. Codd EE, Shank RP, Schupsky JJ, et al. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther 1995 Sep; 274 (3): 1263-70
129. Kreek MJ, Garfield JW, Gutjahr CL, et al. Rifampin-induced methadone withdrawal. N Engl J Med 1976 May 13; 294 (20): 1104-6
130. Baciewicz AM, Self TH. Rifampin drug interactions. Arch Intern Med 1984 Aug; 144 (8): 1667-71
131. Niemi M, Backman JT, Fromm MF, et al. Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet 2003; 42 (9): 819-50
132. Preston KL, Griffiths RR, Stitzer ML, et al. Diazepam and methadone interactions in methadone maintenance. Clin Pharmacol Ther 1984 Oct; 36 (4): 534-41
133. Tong TG, Pond SM, Kreek MJ, et al. Phenytoin-induced methadone withdrawal. Ann Intern Med 1981 Mar; 94 (3): 349-51
134. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother 1995 Jun; 29 (6): 603-9
135. Tarumi Y, Pereira J, Watanabe S. Methadone and fluconazole: respiratory depression by drug interaction. J Pain Symptom Manage 2002 Feb; 23 (2): 148-53
136. Katz HI. Drug interactions of the newer oral antifungal agents. Br J Dermatol 1999 Nov; 141 Suppl. 56: 26-32
137. Eich-Hochli D, Oppliger R, Golay KP, et al. Methadone maintenance treatment and St. John's Wort: a case report. Pharmacopsychiatry 2003 Jan; 36 (1): 35-7
138. Ortega I, Rodriguez M, Suarez E, et al. Modeling methadone pharmacokinetics in rats in presence of p-glycoprotein inhibitor valspodar. Pharm Res 2007 Jul; 24 (7): 1299-308
139. Iribarne C, Picart D, Dreano Y, et al. In vitro interactions between fluoxetine or fluvoxamine and methadone or buprenorphine. Fundam Clin Pharmacol 1998; 12 (2): 194-9
140. Liu SJ, Wang RI. Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome. Am J Psychiatry 1984 Oct; 141 (10): 1287-8
141. Moody DE, Walsh SL, Rollins DE, et al. Ketoconazole, a cytochrome P450 3A4 inhibitor, markedly increases concentrations of levo-acetyl-alpha-methadol in opioid-naive individuals. Clin Pharmacol Ther 2004 Aug; 76 (2): 154-66
142. Cobb MN, Desai J, Brown Jr LS, et al. The effect of fluconazole on the clinical pharmacokinetics of methadone. Clin Pharmacol Ther 1998 Jun; 63 (6): 655-62
143. Iribarne C, Picart D, Dreano Y, et al. Involvement of cytochrome P450 3A4 in N-dealkylation of buprenorphine in human liver microsomes. Life Sci 1997; 60 (22): 1953-64
144. Bart PA, Rizzardi PG, Gallant S, et al. Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir. Ther Drug Monit 2001 Oct; 23 (5): 553-5
145. Clarke SM, Mulcahy FM, Tjia J, et al. The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz. Br J Clin Pharmacol 2001 Mar; 51 (3): 213-7
146. Marzolini C, Troillet N, Telenti A, et al. Efavirenz decreases methadone blood concentrations. AIDS 2000 Jun 16; 14 (9): 1291-2
147. Barry M, Gibbons S, Back D, et al. Protease inhibitors in patients with HIV disease: clinically important pharmacokinetic considerations. Clin Pharmacokinet 1997 Mar; 32 (3): 194-209
148. Beauverie P, Taburet AM, Dessalles MC, et al. Therapeutic drug monitoring of methadone in HIV-infected patients receiving protease inhibitors. AIDS 1998 Dec 24; 12 (18): 2510-1
149. Geletko SM, Erickson AD. Decreased methadone effect after ritonavir initiation. Pharmacotherapy 2000 Jan; 20 (1): 93-4
150. Altice FL, Friedland GH, Cooney EL. Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone. AIDS 1999 May 28; 13 (8): 957-62
151. Otero MJ, Fuertes A, Sanchez R, et al. Nevirapine-induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert. AIDS 1999 May 28; 13 (8): 1004-5
152. Dole VP, Warner A. Selected bibliography on narcotic addiction treatment, 1960-1966: reports of treatment programs. Am J Public Health Nations Health 1967 Nov; 57 (11): 2005-8
153. Mannino R, Coyne P, Swainey C, et al. Methadone for cancer-related neuropathic pain: a review of the literature. J Opioid Manag 2006 Sep-Oct; 2 (5): 269-76
154. Boglione-Kerrien C, Furet Y, Bachellier J, et al. Methadone blood assay by the FPIA technique: application to the monitoring of patients in maintenance treatment to opiates [in French]. Ann Biol Clin (Paris) 2007 Jan-Feb; 65 (1): 51-7
155. Eap CB, Bourquin M, Martin J, et al. Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment. Drug Alcohol Depend 2000 Dec 22; 61 (1): 47-54
156. Maxwell S, Shinderman M. Optimizing response to methadone maintenance treatment: use of higher-dose methadone. J Psychoactive Drugs 1999 Apr-Jun; 31 (2): 95-102
157. Krantz MJ, Lewkowiez L, Hays H, et al. Torsade de pointes associated with very high-dose methadone. Ann Intern Med 2002 Sep 17; 137 (6): 501-4
158. Terpening CM, Johnson WM. Methadone as an analgesic: a review of the risks and benefits. W V Med J 2007 Jan-Feb; 103 (1): 14-8
159. Kornick CA, Kilborn MJ, Santiago-Palma J, et al. QTc interval prolongation associated with intravenous methadone. Pain 2003 Oct; 105 (3): 499-506
160. Bryson J, Tamber A, Seccareccia D, et al. Methadone for treatment of cancer pain. Curr Oncol Rep 2006 Jul; 8 (4): 282-8