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

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 (AUC_0→∞), the maximum plasma concentration (C_max) and the elimination half-life (T_1/2) 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 AUC_0→∞s of metoprolol were 443.7 ± 168.1, 995.6 ± 321.4 and 2545.3 ± 632.0 ng.h/mL, and the AUC_0→∞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 T_1/2 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.