Influence of CYP2D6*10 on the pharmacokinetics of metoprolol in healthy Korean volunteers
- Authors
- Jin, Sun Kyung; Chung, Hye Ju; Chung, Myeon-Woo; Kim, Joo-Il; Kang, Ju-Hee; Woo, Sun-Wook; Bang, Syrie; Lee, Sang-Hun; Lee, Hwa Jeong; Roh, Jaesook
- Issue Date
- Oct-2008
- Publisher
- WILEY
- Keywords
- CYP2D6; Korean; Metoprolol; Pharmacokinetics
- Citation
- JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, v.33, no.5, pp.567 - 573
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
- Volume
- 33
- Number
- 5
- Start Page
- 567
- End Page
- 573
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/177856
- DOI
- 10.1111/j.1365-2710.2008.00945.x
- ISSN
- 0269-4727
- 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((R))) 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, alpha-hydroxymetoprolol, and the metabolic ratio for the three groups were estimated and compared. Results and discussion: The area under the plasma concentration-time curve (AUC(0 ->infinity)), the maximum plasma concentration (C-max) and the elimination half-life (T-1/2) of metoprolol and alpha-hydroxymetoprolol for the CYP2D6*10/*10 group were all significantly different from those of the CYP2D6*1/*1 group (P < 0.05). The AUC(0 ->infinity)s of metoprolol were 443.7 +/- 168.1, 995.6 +/- 321.4 and 2545.3 +/- 632.0 ng.h/mL, and the AUC(0 ->infinity)s of alpha-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 T-1/2 values of metoprolol were 2.7 +/- 0.5, 3.2 +/- 1.3 and 5.0 +/- 1.1 h, while those of alpha-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.
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