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Influence of CYP2D6*10 on the pharmacokinetics of metoprolol in healthy Korean volunteers

Title
Influence of CYP2D6*10 on the pharmacokinetics of metoprolol in healthy Korean volunteers
Authors
Jin S.K.Chung H.J.Chung M.W.Kim J.-I.Kang J.-H.Woo S.W.Bang S.Lee S.H.Lee H.J.Roh J.
Ewha Authors
이화정
SCOPUS Author ID
이화정scopus
Issue Date
2008
Journal Title
Journal of Clinical Pharmacy and Therapeutics
ISSN
0269-4727JCR Link
Citation
vol. 33, no. 5, pp. 567 - 573
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Background and objective: Genetic polymorphism of CYP2D6 leads to differences in pharmacokinetics of CYP2D6 substrates. The CYP2D6*10 allele is clinically important in Koreans because of its high frequency in Asians. We investigated whether the pharmacokinetics of metoprolol was altered by the presence of the CYP2D6*10 allele in Korean subjects. Methods: One hundred and seven volunteers were recruited and grouped as CYP2D6*1/*1, CYP2D6*1/*10 and CYP2D6*10/*10 according to their genotypes. Metoprolol tartrate 100 mg (Betaloc®) was administered orally once to each subject in these three groups (n = 6, 7 and 5, respectively). The pharmacokinetic parameters of metoprolol and its metabolite, α-hydroxymetoprolol, and the metabolic ratio for the three groups were estimated and compared. Results and discussion: The area under the plasma concentration-time curve (AUC0→∞), the maximum plasma concentration (Cmax) and the elimination half-life (T1/2) of metoprolol and α-hydroxymetoprolol for the CYP2D6*10/*10 group were all significantly different from those of the CYP2D6*1/*1 group (P < 0.05). The AUC0→∞s of metoprolol were 443.7 ± 168.1, 995.6 ± 321.4 and 2545.3 ± 632.0 ng.h/mL, and the AUC0→∞s of α-hydroxymetoprolol were 1232.0 ± 311.2, 1344.0 ± 288.1 and 877.4 ± 103.4 ng.h/mL for groups CYP2D6*1/*1, *1/*10 and *10/*10, respectively. The corresponding T1/2 values of metoprolol were 2.7 ± 0.5, 3.2 ± 1.3 and 5.0 ± 1.1 h, while those of α-hydroxymetoprolol were 5.4±1.5, 6.0 ± 1.4 and 10.5 ± 4.2 h, respectively. The metabolic ratios of the three groups were significantly different (P < 0.05). Conclusion: The CYP2D6*10 allele altered the pharmacokinetics of metoprolol in Korean subjects and is likely to affect other drugs metabolized by the CYP2D6 enzyme, similarly. © 2008 The Authors.
DOI
10.1111/j.1365-2710.2008.00945.x
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약학대학 > 약학과 > Journal papers
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