The effect of combined therapy on the pharmacokinetics and pharmacodynamics of verapamil and propranolol in patients with angina pectoris.

1. The pharmacokinetics and pharmacodynamics of oral verapamil and propranolol were studied in patients with stable angina pectoris during chronic mono- and dual therapy. 2. The peak plasma concentrations (Cmax) and areas under the plasma concentration-time curves (AUC) of verapamil were similar during combined treatment with propranolol (mean +/- s.d.: Cmax = 491 +/- 397 ng ml-1; AUC = 2075 +/- 1524 ng ml-1 h) or atenolol (mean +/- s.d.: Cmax = 372 +/- 320 ng ml-1; AUC = 1985 +/- 1660 ng ml-1 h). 3. No differences in Cmax and AUC were observed during verapamil monotherapy (mean +/- s.d.: Cmax = 287 +/- 105 ng ml-1; AUC = 1375 +/- 455 ng ml-1 h) vs combined treatment with propranolol (mean +/- s.d.: Cmax = 312 +/- 55 ng ml-1; AUC = 1566 +/- 486 ng ml-1 h). 4. Treatment with verapamil increased the Cmax (mean +/- s.d.: 227 +/- 117 vs 116 +/- 62 ng ml-1, P less than 0.05) and AUC (1389 +/- 617 vs 837 +/- 316 ng ml-1 h, P = 0.0625) of propranolol in all subjects. 5. Transient atrioventricular dissociation occurred in two patients 2 h after dosing with verapamil and propranolol or atenolol. 6. Close observation of patients is essential when beta-adrenoceptor antagonists and verapamil are used together.