Influence of and Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Bisoprolol in Hypertensive Chinese Patients.

This study was performed to investigate the effects of common polymorphisms in and on the plasma concentrations and antihypertensive effects of bisoprolol in hypertensive Chinese patients. One hundred patients with essential hypertension were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Clinic blood pressure (BP) and ambulatory BP (ABP) were measured after the placebo run-in and after 6 weeks treatment. Peak plasma concentrations of bisoprolol were measured at 3 h after the first dose and 3 h after the dose after 6 weeks treatment. Trough levels were measured before the dose after 6 weeks treatment. Bisoprolol plasma concentrations were measured with a validated liquid chromatography tandem mass spectrometry method. Six common polymorphisms in and the polymorphism were genotyped by TaqMan® assay. After 6 weeks of treatment, clinic BP and heart rate were significantly reduced by 14.3 ± 10.9/8.4 ± 6.2 mmHg ( < 0.01) and 6.3 ± 7.6 BPM ( < 0.01), respectively. Similar reductions were seen in ABP values. Bisoprolol plasma concentration at 3 h after the first dose and 3 h post-dose after 6 weeks of treatment were significantly associated with baseline body weight ( < 0.001) but there was no significant effect of the and polymorphisms on these or the trough plasma concentrations. There was no significant association of the and polymorphisms or plasma bisoprolol concentrations with the clinic BP or ABP responses to bisoprolol. Bisoprolol 2.5 mg daily effectively reduced BP and HR. The common polymorphisms in that were examined and the polymorphism appear to have no benefit in predicting the hemodynamic response to bisoprolol in these patients.