Aim: This study was conducted to determine the metabolic phenotypes of newly discovered CYP2D6 genotypes. Methods: Totally, 22 volunteers were recruited in the study. The peripheral blood and urine were collected at the indicated time after orally administration of 100 mg metoprolol. After sample preparation, a validated HPLC method was employed to determine metoprolol and α-hydroxymetoprolol. Meanwhile, the blood pressure and electrocardiogram of the subjects were monitored. Results: It is demonstrated that the main pharmacokinetic parameters of analytes in CYP2D6*1/*34 were comparable to CYP2D6*1/*1. The AUC and t1/2 of CYP2D6*10/*87, CYP2D6*10/*95 and CYP2D6*97/*97 increased by 2-3 times comparing to wild-type. The urine metabolic rate of metoprolol in these genotypes were in consistence to the tendencies obtained from plasma samples. Therefore, CYP2D6*1/*34 can be assigned as normal metabolizer, while CYP2D6*10/*87, CYP2D6*10/*95 and CYP2D6*97/*97 were intermediate metabolizers. Although the blood concentration of metoprolol is correlated with genotype of CYP2D6, its blood pressure lowering effect is saturated at the maximum efficacy at 25 mmHg. In addition, the P-Q interval prolongation and heart rate lowing were not positively correlated with metoprolol blood exposure. Conclusion: Based on the PK-PD model, this study clarified the pharmacokinetic and pharmacodynamic characteristics of metoprolol with novel CYP2D6 genotypes, and provided a solid basic data for translational medicine of substrate drug.