Enantiospecific pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers and correlation with exercise-induced heart rate

European Journal of Clinical Pharmacology

Volumn 64, Issue 9, 2008, Pages 883-888

  Seeringer, Angela ^a   Brockmöller, Jürgen ^b   Bauer, Steffen ^c   Kirchheiner, Julia ^a  

^a UNIVERSITY OF ULM   (Germany)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Cytochrome P450 enzyme 2D6; Enantioselective metabolism; Metoprolol; Pharmacogenetics; Ultra rapid metabolizer

Indexed keywords

BETA 1 ADRENERGIC RECEPTOR; CYTOCHROME P450 2D6; DRUG METABOLITE; HYDROXYMETOPROLOL; METOPROLOL; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BICYCLE ERGOMETRY; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG BLOOD LEVEL; DRUG METABOLISM; ENANTIOMER; ENANTIOSELECTIVITY; EXERCISE; FEMALE; GENOTYPE; HEART RATE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RACEMIC MIXTURE; SINGLE DRUG DOSE;

ADRENERGIC BETA-ANTAGONISTS; AREA UNDER CURVE; CYTOCHROME P-450 CYP2D6; EXERCISE; EXERCISE TEST; GENOTYPE; HEART RATE; HUMANS; METOPROLOL; PHARMACOGENETICS; STATISTICS, NONPARAMETRIC; STEREOISOMERISM;

EID: 50849134614     PISSN: 00316970     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00228-008-0504-8     Document Type: Article

References (17)

1. J Kirchheiner C Heesch S Bauer 2004 Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on metoprolol pharmacokinetics and pharmacodynamics Clin Pharmacol Ther 76 302
2. H Wuttke T Rau R Heide 2002 Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects Clin Pharmacol Ther 72 429
3. PA Thurmann S Haack U Werner 2006 Tolerability of beta-blockers metabolized via cytochrome P450 2D6 is sex-dependent Clin Pharmacol Ther 80 551
4. I Johansson E Lundqvist L Bertilsson 1993 Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine Proc Natl Acad Sci USA 90 11825
5. R Fux K Morike AM Prohmer 2005 Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study Clin Pharmacol Ther 78 378
6. I Zineh AL Beitelshees A Gaedigk 2004 Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension Clin Pharmacol Ther 76 536
7. MS Lennard GT Tucker JH Silas 1983 Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers Clin Pharmacol Ther 34 732
8. JH Silas JC McGourty MS Lennard 1985 Polymorphic metabolism of metoprolol: clinical studies Eur J Clin Pharmacol 28 Suppl 85
9. MS Lennard GT Tucker JH Silas 1986 Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol Xenobiotica 16 435
10. P Dayer T Leemann A Marmy 1985 Interindividual variation of beta-adrenoceptor blocking drugs, plasma concentration and effect: influence of genetic status on behaviour of atenolol, bopindolol and metoprolol Eur J Clin Pharmacol 28 149
11. RE Jonkers RP Koopmans EJ Portier 1991 Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers J Pharmacol Exp Ther 256 959
12. PM Cerqueira EJ Cesarino C Bertucci 2003 Stereoselective metabolism of metoprolol: enantioselectivity of alpha-hydroxymetoprolol in plasma and urine Chirality 15 542
13. JA Johnson BS Burlew 1996 Metoprolol metabolism via cytochrome P4502D6 in ethnic populations Drug Metab Dispos 24 350
14. A Hemeryck RA Lefebvre C De Vriendt 2000 Paroxetine affects metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers Clin Pharmacol Ther 67 283
15. PM Cerqueira EJ Cesarino FH Mateus 1999 Enantioselectivity in the steady-state pharmacokinetics of metoprolol in hypertensive patients Chirality 11 591
16. MS Lennard 1985 Oxidation phenotype and the metabolism and action of beta-blockers Klin Wochenschr 63 285
17. DW Clark AK Morgan H Waal-Manning 1984 Adverse effects from metoprolol are not generally associated with oxidation status Br J Clin Pharmacol 18 965