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Dtsch Med Wochenschr 2004; 129(15): 831-835
DOI: 10.1055/s-2004-823030
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Pharmakologie / Kardiologie
© Georg Thieme Verlag Stuttgart · New York

Genpolymorphismen in Arzneimittel-abbauenden Enzymen

Bedeutung für die Therapie mit β-BlockernGenetic polymorphisms in drug metabolizing enzymesImpact on treatment with β-blockersH. Wuttke1 , T. Rau1 , T. Eschenhagen1
  • 1Institut für Experimentelle und Klinische Pharmakologie, Universitätsklinikum Hamburg-Eppendorf
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Publikationsverlauf

eingereicht: 9.2.2004

akzeptiert: 18.3.2004

Publikationsdatum:
31. März 2004 (online)

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Glossar

CYP: Cytochrom P450

EM: Extensive metabolizer (normale metabolische Aktivität)

IM: Intermediate metabolizer (reduzierte metabolische Aktivität)

PM: Poor metabolizer (keine metabolische Aktivität)

UAW: Unerwünschte Arzneimittelwirkung

UM: Ultrarapid metabolizer (gesteigerte metabolische Aktivität)

Literatur

  • 1 Abrahamsson B, Lücker P, Olofsson B. et al . The relationship between metoprolol plasma concentration and beta 1-blockade in healthy subjects: a study on conventional metoprolol and metoprolol CR/ZOK formulations.  J Clin Pharmacol. 1990;  30 S46-S54
    Suche in Google Scholar
  • 2 BERLIN-CHEMIE AG .Fachinformation Nebilet®;. 2003
    Suche in Google Scholar
  • 3 Cheymol G, Woestenborghs R, Snoeck E. et al . Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects.  Eur J Clin Pharmacol. 1997;  51 493-498
    Suche in Google Scholar
  • 4 Clark D W, Morgan A K, Waal-Manning H. Adverse effects from metoprolol are not generally associated with oxidation status.  Br J Clin Pharmacol. 1984;  18 965-967
    Suche in Google Scholar
  • 5 Collette D, Thürmann P A. Unerwünschte Arzneimittelwirkungen. Erbliche Unterschiede im Arzneistoffmetabolismus.  Dtsch Med Wochenschr. 2002;  127 1025-1028
    Suche in Google Scholar
  • 6 Dahl M L, Johansson I, Bertilsson L, Ingelman-Sundberg M, Sjöqvist F. Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis.  J Pharmacol Exp Ther. 1995;  274 516-520
    Suche in Google Scholar
  • 7 Deroubaix X, Lins R L, Lens S. et al . Comparative bioavailability of a metoprolol controlled release formulation and a bisoprolol normal release tablet after single oral dose administration in healthy volunteers.  Int J Clin Pharmacol Ther. 1996;  34 61-70
    Suche in Google Scholar
  • 8 Eichelbaum M, Burk O. CYP3A genetics in drug metabolism.  Nat Med. 2001;  7 285-287
    Suche in Google Scholar
  • 9 Eichelbaum M, Spannbrucker N, Steincke B, Dengler H J. Defective N-oxidation of sparteine in man: a new pharmacogenetic defect.  Eur J Clin Pharmacol. 1979;  16 183-187
    Suche in Google Scholar
  • 10 Evans W E, McLeod H L. Pharmacogenomics - drug disposition, drug targets, and side effects.  N Engl J Med. 2003;  348 538-549
    Suche in Google Scholar
  • 11 Gottlieb S S, Fisher M L, Kjekshus J. et al . Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF).  Circulation. 2002;  105 1182-1188
    Suche in Google Scholar
  • 12 Graff D W, Williamson K M, Pieper J A. et al . Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure patients.  J Clin Pharmacol. 2001;  41 97-106
    Suche in Google Scholar
  • 13 Griese E U, Zanger U M, Brudermanns U. et al . Assessment of the predictive power of genotypes for the in-vivo catalytic function of CYP2D6 in a German population.  Pharmacogenetics. 1998;  8 15-26
    Suche in Google Scholar
  • 14 Horikiri Y, Suzuki T, Mizobe M. Stereoselective metabolism of bisoprolol enantiomers in dogs and humans.  Life Sci. 1998;  63 1097-1108
    Suche in Google Scholar
  • 15 Human Allele Nomenclature Committee .Home Page of the Human Cytochrome P450 (CYP). http://www.imm.ki.se/CYPalleles/ 2004
    Suche in Google Scholar
  • 16 Ingelman-Sundberg M. Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms.  Naunyn Schmiedebergs Arch Pharmacol. 2004;  369 89-104
    Suche in Google Scholar
  • 17 Keating G M, Jarvis B. Carvedilol: a review of its use in chronic heart failure.  Drugs. 2003;  63 1697-1741
    Suche in Google Scholar
  • 18 Komajda M, Follath F, Swedberg K. et al . The EuroHeart Failure Survey programme - a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment.  Eur Heart J. 2003;  24 464-474
    Suche in Google Scholar
  • 19 Lacourciere Y, Poirier L, Lefebvre J, Archambault F, Cleroux J. Comparative assessment of antihypertensive efficacy of DL-nebivolol and D-nebivolol in patients with confirmed mild to moderate hypertension.  J Cardiovasc Pharmacol. 1995;  25 619-624
    Suche in Google Scholar
  • 20 Lamba J K, Lin Y S, Schuetz E G, Thummel K E. Genetic contribution to variable human CYP3A-mediated metabolism.  Adv Drug Deliv Rev. 2002;  54 1271-1294
    Suche in Google Scholar
  • 21 Leineweber K, Büscher R, Bruck H, Brodde O E. beta-Adrenoceptor polymorphisms.  Naunyn Schmiedebergs Arch Pharmacol. 2004;  369 1-22
    Suche in Google Scholar
  • 22 Lemmer B. Betarezeptorenblocker. Berlin Heidelberg: Springer-Verlag In: Schwabe U, Paffrath D, editors. Arzneiverordnungsreport 2001 2001: 287-296
    Suche in Google Scholar
  • 23 Lennard M S, Silas J H, Freestone S, Ramsay L E, Tucker G T, Woods H F. Oxidation phenotype - a major determinant of metoprolol metabolism and response.  N Engl J Med. 1982;  307 1558-1560
    Suche in Google Scholar
  • 24 Lennard M S, Tucker G T, Silas J H, Woods H F. Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol.  Xenobiotica. 1986;  16 435-447
    Suche in Google Scholar
  • 25 Leopold G. Balanced pharmacokinetics and metabolism of bisoprolol.  J Cardiovasc Pharmacol. 1986;  8 S16-20
    Suche in Google Scholar
  • 26 Lohse M J, Engelhardt S, Eschenhagen T. What is the role of beta-adrenergic signaling in heart failure?.  Circ Res. 2003;  93 896-906
    Suche in Google Scholar
  • 27 Mahgoub A, Idle J R, Dring L G, Lancaster R, Smith R L. Polymorphic hydroxylation of Debrisoquine in man.  Lancet. 1977;  2 584-586
    Suche in Google Scholar
  • 28 McNeely W, Goa K L. Nebivolol in the management of essential hypertension: a review.  Drugs. 1999;  57 633-651
    Suche in Google Scholar
  • 29 Meyer U A. Pharmacogenetics and adverse drug reactions.  Lancet. 2000;  356 1667-1671
    Suche in Google Scholar
  • 30 Raimundo S, Fischer J, Eichelbaum M, Griese E U, Schwab M, Zanger U M. Elucidation of the genetic basis of the common ‘intermediate metabolizer’ phenotype for drug oxidation by CYP2D6.  Pharmacogenetics. 2000;  10 577-581
    Suche in Google Scholar
  • 31 Rau T, Heide R, Bergmann K. et al . Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment.  Pharmacogenetics. 2002;  12 465-472
    Suche in Google Scholar
  • 32 Roden D M. Cardiovascular pharmacogenomics.  Circulation. 2003;  108 3071-3074
    Suche in Google Scholar
  • 33 Sachse C, Brockmöller J, Bauer S, Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences.  Am J Hum Genet. 1997;  60 284-295
    Suche in Google Scholar
  • 34 Siddoway L A, Thompson K A, McAllister C B. et al . Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences.  Circulation. 1987;  75 785-791
    Suche in Google Scholar
  • 35 Van Rooy P, De Crée J. Haemodynamic effects of nebivolol in poor and extensive metabolisers.  Drug Investig. 1991;  3 161-163
    Suche in Google Scholar
  • 36 Wadworth A N, Murdoch D, Brogden R N. Atenolol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders.  Drugs. 1991;  42 468-510
    Suche in Google Scholar
  • 37 Wagner F, Kalusche D, Trenk D, Jähnchen E, Roskamm H. Drug interaction between propafenone and metoprolol.  Br J Clin Pharmacol. 1987;  24 213-220
    Suche in Google Scholar
  • 38 Wuttke H, Rau T, Heide R. et al . Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects.  Clin Pharmacol Ther. 2002;  72 429-437
    Suche in Google Scholar
  • 39 Zanger U M, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry.  Naunyn Schmiedebergs Arch Pharmacol. 2004;  369 23-37
    Suche in Google Scholar
  • 40 Zhou H H, Wood A J. Stereoselective disposition of carvedilol is determined by CYP2D6.  Clin Pharmacol Ther. 1995;  57 518-524
    Suche in Google Scholar

Prof. Dr. med. Thomas Eschenhagen

Institut für Experimentelle und Klinische Pharmakologie, Universitätsklinikum Hamburg-Eppendorf

Martinistraße 52

20246 Hamburg

Telefon: +49/40/428033180

Fax: +49/40/428034876

eMail: t.eschenhagen@uke.uni-hamburg.de