Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol

European Journal of Clinical Pharmacology

Volumn 53, Issue 3-4, 1997, Pages 235-239

  Paar, W D ^a   Poche, S ^a   Gerloff, J ^b   Dengler, H J ^a  

^a UNIVERSITY OF BONN   (Germany)

^b GRÜNENTHAL GMBH   (Germany)

Author keywords

CYP2D6; Tramadol

Indexed keywords

CYTOCHROME P450 ISOENZYME; DRUG METABOLITE; SPARTEINE SULFATE; TRAMADOL;

ADULT; ARTICLE; CLINICAL TRIAL; DEMETHYLATION; DRUG EXCRETION; DRUG METABOLISM; FEMALE; GENETIC POLYMORPHISM; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PHARMACOKINETICS; PHENOTYPE; PRIORITY JOURNAL; TABLET; VOLUNTEER;

ADULT; ANALGESICS, OPIOID; CYTOCHROME P-450 CYP2D6; DEALKYLATION; FEMALE; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, GENETIC; SPARTEINE; TRAMADOL;

EID: 0031460240     PISSN: 00316970     EISSN: None     Source Type: Journal    
DOI: 10.1007/s002280050368     Document Type: Article

References (16)

1. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL (1992) Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. J Pharmacol Exp Ther 260: 275-285
2. Friderichs E, Reimann W, Selve N (1992) Contribution of both enantiomers to the antinociception of the centrally acting analgesic tramadol. Naunyn Schmiedebergs Arch Pharmacol 346: R36 (abstr.)
3. Collard L, Luthy C, Dayer P (1994) (±)-Tramadol concentration-effect relationship. Clin Pharmacol Ther 55: 208 (abstr.)
4. Lintz W, Barth H, Osterloh G, Schmidt-Böthelt E (1986) Bioavailability of enteral tramadol formulations. Arzneimittellbrschung 636: 1278-1283
5. Lintz W, Erlacin S, Frankus E, Uragg H (1981) Metabolismus von Tramadol bei Mensch und Tier. Arzneimittelforschung 31: 1932-1943
6. Friderichs E, Becker R (1991) Correlation of tramadol and Ml serum levels with antinociceptive activity in mice. Naunyn Schmiedebergs Arch Pharmacol 343: 9 (abstr.)
7. Paar WD, Frankus P, Dengler HJ (1992) The metabolism of tramadol by human liver microsomes. Clin Investig 70: 708-710
8. Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16: 183-87
9. Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL (1977) Polymorphic hydroxylation of debrisoquine in man. Lancet 2: 584-586
10. Lledó P (1993) Variations in drug metabolism due to genetic polymorphism. A review of the debrisoquine/sparteine type. Drug Invest 5: 19-34
11. Dayer P, Desmeules J, Leemann T, Striberni R (1988) Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufl). Biochem Biophys Res Commun 152: 411-416
12. Becker R, Lintz W (1986) Determination of tramadol in human serum by capillary gas chromatography with nitrogen selective detection. J Chromatogr 377: 213-220
13. Heim M, Meyer UA (1990) Genotyping of poor metabolizers of debrisoquine by allele-specific PCR amplification. Lancet 336: 529-532
14. Hamm S, von Unruh GE, Paar WD, Dengler HJ (1994) Isotope effects during metabolism of (+/-)-tramadol isotopomers by human liver microsomes. Isotopenpraxis Environ Health Stud 30: 99-110
15. Jackson PR, Tucker GT, Lennard MS, Woods HF (1986) Polymorphic drug oxidation: pharmacokinetic basis and comparison of experimental indices. Br J Clin Pharmacol 22: 541 540
16. Poulsen L, Arendt-Nielsen L, Brosen K, Sindrup SH (1996) The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther 60: 636-644