Pharmacokinetics and pharmacodynamics of verapamil in combination with atenolol, metoprolol and propranolol.

Treatment of angina pectoris with beta-adrenoceptor antagonists and verapamil in combination is effective and increasingly common. The study reported here was designed to show whether the pharmacokinetics of verapamil are influenced by concurrent treatment with three different beta-adrenoceptor blockers, and whether there is any pharmacodynamic interaction between these drugs. Twelve healthy volunteers (eight men, four women) aged 21-25 years and weighing 48-82 kg consented to participate in the study. They received verapamil 50 mg three times daily for four 1-week periods, each separated by a 1 week 'washout' period. During three of the four treatment periods, the subjects took either atenolol 100 mg once daily, metoprolol 100 mg twice daily or propranolol 80 mg twice daily; in the remaining period they took verapamil alone. The concentration/time curve and plasma elimination half-life of verapamil and norverapamil, its major metabolite, were not influenced by 1 weeks co-administration atenolol, metoprolol or propranolol. As expected, co-administration of each of the beta-adrenoceptor blockers significantly reduced exercise heart rate when compared with verapamil alone.