| Autor: |
H. Henckel, Julia Kirchheiner, Steffen Bauer, Ivar Roots, C. Meisel, J. Brockmöller, T. Keulen, C. Heesch |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Clinical Pharmacology & Therapeutics. 75:P19 |
| ISSN: |
0009-9236 |
| DOI: |
10.1016/j.clpt.2003.11.070 |
| Popis: |
The influence of CYP2D6 gene duplications (ultrarapid metabolism) on metoprolol pharmacokinetics and on its action on exercise heart rate was studied in studied in 9 healthy volunteers carrying CYP2D6 duplications and 8 individuals with CYP2D6 wild-type. Metoprolol and hydroxymetoprolol plasma concentrations were determined after 100 mg normal release metoprolol (Metoprolol-Ratiopharm, Ulm, Germany) by high-pressure liquid chromatography. Exercise electrocardiography was performed for 4 min at a work load sufficient to achieve a heart rate of 140/min without metoprolol and after intake of metoprolol. Beta-blockade was expressed as percentage reduction of heart rate directly after exercise. Mean metoprolol AUC was 627 μg · h/L (standard deviation 347μg · h/L) in extensive metabolizers and 326 μg · h/L (143μg · h/L) in ultra-rapid metabolizers. AUCs of the hydroxy-metabolite were slightly (11%) higher in the ultra-rapid metabolizers but group differences were not statistically significant. All participants showed an about 20% reduced heart rate under exercise at 2 h after metoprolol intake but there was no significant difference in percentage of reduction in exercise heart-rate between the metabolizer groups. In conclusion, carriers of the CYP2D6 gene duplications predicting ultrarapid metabolism showed an about twofold increase in oral clearance of metoprolol in contrast to extensive metabolizer with two active alleles. Clinical Pharmacology & Therapeutics (2004) 75, P19–P19; doi: 10.1016/j.clpt.2003.11.070 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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