Pharmakogenetik in der Kardiologie

Springer Science and Business Media LLC - Tập 1 - Trang 272-280 - 2007
I. Cascorbi1
1Institut für Pharmakologie, Universitätsklinikum Schleswig-Holstein, Kiel, Deutschland

Tóm tắt

Die Effektivität und Sicherheit von Arzneimitteln weist eine große interindividuelle Variabilität auf. Für einige spielt dabei die Pharmakogenetik eine wichtige Rolle. Im Bereich der Antikoagulation konnte zuletzt in prospektiven Studien gezeigt werden, dass die Berücksichtung genetischer Marker bei der Dosierung des Vitamin-K-Antagonisten Warfarin die Effektivität und Sicherheit in Hinblick auf das Blutungsrisiko und die INR-Stabilisierung deutlich verbessern kann. Auch in wenigen anderen Bereichen deutet sich an, dass die individualisierte Pharmakotherapie den klinischen Verlauf günstig beeinflussen könnte, oft mangelt es aber noch an prospektiven Studien. Dieser Übersichtsbeitrag beleuchtet die Bedeutung genetischer Varianten für die Pharmakokinetik und -dynamik und die Möglichkeiten und Limitationen der klinischen Anwendung in den ausgewählten kardiologischen Therapiefeldern Antikoagulation, Herzinsuffizienz und Hypercholesterinämie.

Tài liệu tham khảo

Samani NJ, Erdmann J, Hall AS et al. (2007) Genomewide association analysis of coronary artery disease. N Engl J Med (in press) Eichelbaum M, Spannbrucker N, Steincke B et al. (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16: 183–187 Mahgoub A, Idle JR, Dring LG et al. (1977) Polymorphic hydroxylation of Debrisoquine in man. Lancet 2: 584–586 Inglis SC, Herbert MK, Davies BJ et al. (2007) Effect of CYP2D6 metabolizer status on the disposition of the (+) and (–) enantiomers of perhexiline in patients with myocardial ischaemia. Pharmacogenet Genomics 17: 305–312 Darbar D, Roden DM (2006) Pharmacogenetics of antiarrhythmic therapy. Expert Opin Pharmacother 7: 1583–1590 Lee JT, Kroemer HK, Silberstein DJ et al. (1990) The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med 322: 1764–1768 Kannankeril PJ, Roden DM (2007) Drug-induced long QT and torsade de pointes: recent advances. Curr Opin Cardiol 22: 39–43 Schmidt GA, Hoehns JD, Purcell JL et al. (2007) Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir. J Am Board Fam Med 20: 411–416 Rau T, Heide R, Bergmann K et al. (2002) Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment. Pharmacogenetics 12: 465–472 Wuttke H, Rau T, Heide R et al. (2002) Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. Clin Pharmacol Ther 72: 429–437 Clark DW, Morgan AK, Waal-Manning H (1984) Adverse effects from metoprolol are not generally associated with oxidation status. Br J Clin Pharmacol 18: 965–967 Zineh I, Beitelshees AL, Gaedigk A et al. (2004) Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Clin Pharmacol Ther 76: 536–544 Fux R, Morike K, Prohmer AM et al. (2005) Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study. Clin Pharmacol Ther 78: 378–387 Giessmann T, Modess C, Hecker U et al. (2004) CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects. Clin Pharmacol Ther 75: 213–222 Hein L (2001) Physiological significance of beta-adrenergic receptor polymorphisms: in-vivo or in-vitro veritas? Pharmacogenetics 11: 187–189 Mason DA, Moore JD, Green SA et al. (1999) A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem 274: 12670–12674 Rathz DA, Brown KM, Kramer LA et al. (2002) Amino acid 49 polymorphisms of the human beta1-adrenergic receptor affect agonist-promoted trafficking. J Cardiovasc Pharmacol 39: 155–160 Leineweber K, Buscher R, Bruck H et al. (2004) Beta-adrenoceptor polymorphisms. Naunyn Schmiedebergs Arch Pharmacol 369: 1–22 Brodde OE (2007) Beta-adrenoceptor blocker treatment and the cardiac beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure. Naunyn Schmiedebergs Arch Pharmacol 374: 361–372 Wagoner LE, Craft LL, Zengel P et al. (2002) Polymorphisms of the beta1-adrenergic receptor predict exercise capacity in heart failure. Am Heart J 144: 840–846 Buscher R, Belger H, Eilmes KJ et al. (2001) In-vivo studies do not support a major functional role for the Gly389Arg beta 1-adrenoceptor polymorphism in humans. Pharmacogenetics 11: 199–205 Liu J, Liu ZQ, Tan ZR et al. (2003) Gly389Arg polymorphism of beta1-adrenergic receptor is associated with the cardiovascular response to metoprolol. Clin Pharmacol Ther 74: 372–379 White HL, De Boer RA, Maqbool A et al. (2003) An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study. Eur J Heart Fail 5: 463–468 Beitelshees AL, Zineh I, Yarandi HN et al. (2006) Influence of phenotype and pharmacokinetics on beta-blocker drug target pharmacogenetics. Pharmacogenomics J 6: 174–178 Brodde OE, Leineweber K (2005) Beta2-adrenoceptor gene polymorphisms.Pharmacogenet Genomics 15:267–275. Wagoner LE, Craft LL, Singh B et al. 2000; Polymorphisms of the beta(2)-adrenergic receptor determine exercise capacity in patients with heart failure. Circ Res 86: 834–840 Lanfear DE, Jones PG, Marsh S et al. (2005) Beta2-adrenergic receptor genotype and survival among patients receiving beta-blocker therapy after an acute coronary syndrome. JAMA 294: 1526–1533 Bruck H, Schwerdtfeger T, Toliat M et al. (2007) Presynaptic alpha-2C adrenoceptor-mediated control of noradrenaline release in humans: genotype- or age-dependent? Clin Pharmacol Ther (in press) Hallberg P, Karlsson J, Kurland L et al. (2002) The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. J Hypertens 20: 2089–2093 Lee CR, Pieper JA, Hinderliter AL et al. (2003) Losartan and E3174 pharmacokinetics in cytochrome P450 2C9*1/*1, *1/*2, and *1/*3 individuals. Pharmacotherapy 23: 720–725 Sekino K, Kubota T, Okada Y et al. (2003) Effect of the single CYP2C9*3 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects. Eur J Clin Pharmacol 59: 589–592 The Digitalis Investigation Group (1997) The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 336: 525–533 Ahmed A, Pitt B, Rahimtoola SH et al. (2007) Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial. Int J Cardiol (in press) Zhang Y, Benet LZ (2001) The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein. Clin Pharmacokinet 40: 159–168 Hoffmeyer S, Burk O, von Richter O et al. (2000) 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 USA 97: 3473–3478 Cascorbi I (2006) Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs. Pharmacol Ther 112: 457–473 Williams D, Feely J (2002) Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 41: 343–370 Kirchheiner J, Kudlicz D, Meisel C et al. (2003) Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (–)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers. Clin Pharmacol Ther 74: 186–194 Mwinyi J, Johne A, Bauer S et al. (2004) Evidence for inverse effects of OATP-C (SLC21A6) 5 and 1b haplotypes on pravastatin kinetics. Clin Pharmacol Ther 75: 415–421 Niemi M, Schaeffeler E, Lang T et al. (2004) High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics 14: 429–440 Maitland-van der Zee AH, Boerwinkle E (2005) Pharmacogenetics of response to statins: where do we stand? Curr Atheroscler Rep 7: 204–208 Mangravite LM, Thorn CF, Krauss RM (2006) Clinical implications of pharmacogenomics of statin treatment. Pharmacogenomics J 6: 360–374 Aithal GP, Day CP, Kesteven PJ et al. (1999) Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 353: 717–719 Sconce EA, Khan TI, Wynne HA et al. (2005) The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 106: 2329–2333 Wadelius M, Pirmohamed M (2007) Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J 7: 99–111 Carlquist JF, Horne BD, Muhlestein JB et al. (2006) Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study. J Thromb Thrombolysis 22: 191–197 Muszkat M, Blotnik S, Elami A et al. (2007) Warfarin metabolism and anticoagulant effect: a prospective, observational study of the impact of CYP2C9 genetic polymorphism in the presence of drug-disease and drug-drug interactions. Clin Ther 29: 427–437 Caraco Y, Blotnick S, Muszkat M (2007) CYP2C9 Genotype-guided Warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin Pharmacol Ther (in press) Ufer M (2005) Effects of CYP2C9 polymorphisms on phenprocoumon anticoagulation status. Clin Pharmacol Ther 77: 335–336 Penning-van Beest F, Erkens J, Petersen KU et al. (2005) Main comedications associated with major bleeding during anticoagulant therapy with coumarins. Eur J Clin Pharmacol 61: 439–444 Hulot JS, Bura A, Villard E et al. (2006) Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108: 2244–2247 Wojnowski L, Kulle B, Schirmer M et al. (2005) NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 112: 3754–3762 Altman RB (2007) PharmGKB: a logical home for knowledge relating genotype to drug response phenotype. Nat Genet 39: 426 Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286: 487–491 Small KM, Wagoner LE, Levin AM et al. (2002) Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure. N Engl J Med 347: 1135–1142 Liggett SB (2000) Pharmacogenetics of beta-1- and beta-2-adrenergic receptors. Pharmacology 61: 167–173 Klein TE, Chang JT, Cho MK et al. (2001) Integrating genotype and phenotype information: an overview of the PharmGKB project. Pharmacogenetics Research Network and Knowledge Base. Pharmacogenomics J 1: 167–170