ABSTRACT
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.
