Pharmacokinetics of tramadol enantiomers and their respective phase I metabolites in relation to CYP2D6 phenotype

Pharmacological Research

Volumn 55, Issue 2, 2007, Pages 122-130

  García Quetglas, Emilio ^a   Azanza, José Ramón ^a   Sádaba, Belén ^a   Muñoz, María José ^a   Gil, Isabel ^a   Campanero, Miguel Angel ^a  

^a UNIVERSITY CLINIC OF NAVARRA   (Spain)

Author keywords

CYP2D6; Enantiomers; M1; M2; Pharmacokinetics; Tramadol

Indexed keywords

ADOLONTA; ADRENALIN; CYTOCHROME P450 2D6; TRAMADOL; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BIOTRANSFORMATION; DISEASE SEVERITY; DIZZINESS; DRUG BLOOD LEVEL; DRUG METABOLISM; ENANTIOMER; FEMALE; HUMAN; MALE; METABOLITE; METHYLATION; MUSCLE HYPOTONIA; NAUSEA; NORMAL HUMAN; PHENOTYPE; PRIORITY JOURNAL; VERTIGO; VOLUNTEER;

ADULT; ANALGESICS, OPIOID; AREA UNDER CURVE; CYTOCHROME P-450 CYP2D6; EPINEPHRINE; FEMALE; HUMANS; MALE; METABOLIC DETOXICATION, PHASE I; PHENOTYPE; POLYMORPHISM, GENETIC; STEREOISOMERISM; TRAMADOL;

EID: 33846598505     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2006.11.003     Document Type: Article

References (35)

1. Raffa R.B., Friderichs E., Reimann W., Shank R.P., Codd E.E., Vaught J.L., et al. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 260 (1992) 275-285
2. Raffa R.B., Friderichs E., Reimann W., Shank R.P., Codd E.E., Vaught J.L., et al. Complementary and synergistic antinoceptive interaction between the enantiomers of tramadol. J Pharmacol Exp Ther 267 (1992) 331-340
3. Grond S., Meuser T., Zech D., Hennig U., and Lehmann K.A. Analgesic efficacy and safety of tramadol enantiomers in comparison with the racemate: a randomised, double-blind study with gynaecological patients using intravenous patient-controlled analgesia. Pain 62 (1995) 313-320
4. Grond S., Zech D., Lynch J., Schug S., and Lehmann K.A. Tramadol-a weak opioid for relief of cancer pain. Pain Clinic 5 (1992) 241-247
5. Rhoda Lee C., Mctavish D., and Sorkin E.M. Tramadol: a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in acute and chronic pain states. Drugs 46 (1994) 313-340
6. Dayer P., Collart L., and Desmeules J. The pharmacology of tramadol. Drugs 47 Suppl 1 (1994) 3-7
7. Gibson T.P. Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. Am J Med 101 Suppl A (1996) 47S-53S
8. Driessen B., Reimann W., and Giertz H. Effects of the central analgesic tramadol on the uptake and release of noradrenaline and in vitro. Br J Pharmacol 108 (1993) 806-811
9. Frankus E., Friderichs E., Felgenhauer F., Kim S.M., and Osterloh G. Über die Isomerentrennung, Strukturaufklärung und pharmalologische charakterisierung von 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-ciclohexan-1-ol. Arzneimittel-Forschung 28 (1978) 114-121
10. Subrahmanyam V., Renwick A.B., Walters D.G., Young P.J., Price R.J., Tonelli A.P., et al. Identification of cytochrome p-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos 29 (2001) 1146-1155
11. Kagimoto M., Heim M., Kagimoto K., Zeugin T., and Meyer U.A. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. J Biol Chem 5 265 (1990) 17209-17214
12. Kimura S., Umeno M., Skoda R.C., Meyer U.A., and Gonzalez F.J. The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. Am J Hum Genet 45 (1989) 889-904
13. Sachse C., Brockmoller J., Bauer S., and Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 60 (1997) 284-295
14. Dalen P., Dahl M.L., Eichelbaum M., Bertilsson L., and Wilkinson G.R. Disposition of debrisoquine in Caucasians with different CYP2D6-genotypes including those with multiple genes. Pharmacogenetics 9 (1999) 697-706
15. Pedersen R.S., Damkier P., and Brosen K. Tramadol as a new probe for cytochrome P450 D6 phenotyping: a population study. Clin Pharmacol Ther 77 6 (2005) 458-467
16. Borlak J., Hermann R., Erb K., and Thum T. A rapid and simple CYP2D6 genotyping assay. A case study with the analgesic tramadol. Metabolism 52 (2003) 1439-1443
17. Gan S.H., Ismail R., Wan Adnan W.A., and Wan Z. Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects. J Pharm Biomed Anal 30 (2002) 189-195
18. Laugesen S., Enggaard T.P., Pedersen R.S., Sindrup S.H., and Brosen K. Paroxetine a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol. Clin Pharmacol Ther 77 4 (2005) 312-323
19. Hui-Chen L., Yang Y., Na W., Ming D., Jian-Fang L., and Hong-Yuan X. Pharmacokinetics of the enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in healthy male and female Chinese volunteers. Chirality 16 (2004) 112-118
20. Liu H.C., Liu T.J., Yang Y.Y., and Hou Y.N. Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in human subjects. Acta Pharmacol Sin 22 (2001) 91-96
21. Fliegert F., Kurth B., and Gohler K. The effects of tramadol on static and dynamic pupillometry in healthy subjects-the relationship between pharmacodynamics, pharmacokinetics and CYP2D6 metaboliser status. Eur J Clin Pharmacol 61 (2005) 257-266
22. Pedersen R.S., Damkier P., and Brosen K. Enantioselective pharmacokinetics of tramadol in CYP2D6 extensive and poor metabolizers. Eur J Clin Pharmacol 62 (2006) 513-521
23. Campanero M.A., Garcia-Quetglas E., Sadaba B., and Azanza J.R. Simultaneous stereoselective analysis of tramadol and its primary phase I metabolites in plasma by liquid chromatography: application to a pharmacokinetic study in humans. J Chromatogr A 1031 (2004) 265-273
24. Novalbos J., Ladona M.G., Gallego S., Galvez M.A., Garcia A.G., and Abad Santos F. Are healthy volunteers an adequate population for the study of genetic polymorphism of CYP2D6?. Rev Med Univ Navarra 13 (2003) 25
25. Hogger P. Adverse effects of opioid analgesic treatment are correlated with a significant elevation in plasma epinephrine in healthy humans. Eur J Clin Pharmacol 56 (2000) 463-468
26. Fliegert F., Kurth B., and Gohler K. Impact of the CYP2D6 metaboliser status on the pupillary response of tramadol-a commentary. Eur J Clin Pharmacol 62 1 (2006) 77-78
27. Slanar O., Nobilis M., Kvetina J., Idle J.R., and Perlik F. CYP2D6 polymorphism, tramadol pharmacokinetics and pupillary response. Eur J Clin Pharmacol 62 1 (2006) 75-76
28. Slanar O, Nobilis M, Kvetina J, Mikoviny R, Zima T, Idle JR, et al. Miotic action of tramadol is determined by CYP2D6 genotype. Physiol Res, 2006.
29. Enggaard T.P., Poulsen L., Arendt-Nielsen L., Brosen K., Ossig J., and Sindrup S.H. The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6. Anesth Analg 102 1 (2006) 146-150
30. Levo A., Koski A., Ojanpera I., Vuori E., and Sajantila A. Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) metabolite ratios in blood. Forensic Sci Int 135 (2003) 9-15
31. Mildh L.H., Leino K.A., and Kirvela O.A. Effects of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamics. J Clin Anesth 11 (1999) 310-316
32. Garrido M.J., Sayar O., Segura C., Rapado J., Dios-Vieitez M.C., Renedo M.J., et al. Pharmacokinetic/pharmacodynamic modeling of the antinociceptive effects of (+)-tramadol in the rat: role of cytochrome P450 2D activity. J Pharmacol Exp Ther 305 (2003) 710-718
33. Grond S., Meuser T., Uragg H., Stahlberg H.J., and Lehmann K.A. Serum concentrations of tramadol enantiomers during patient-controlled analgesia. Br J Clin Pharmacol 48 (1999) 254-257
34. Stamer U.M., Lehnen K., Hothker F., Bayerer B., Wolf S., Hoeft A., et al. Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain 105 (2003) 231-238
35. Poulsen L., Arendt-Nielsen L., Brosen K., and Sindrup S.H. The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther 60 (1996) 637-644