THE PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTIONS OF RAMIPRIL WITHPROPRANOLOL

We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pha rmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 7 2 (7) kg). Propranolol and placebo, ramipril and placebo, or propranol ol and ramipril were given orally for four days in a crossover, double -blind fashion. The pharmacokinetics of ramipril and ramiprilat were i nvestigated on day 4. Effects on plasma renin activity, ACE activity, and heart rate and blood pressure both before and after a standardized exercise test were measured on days 1 and 4. On day 4 the combination reduced the mean arterial pressure by 2.8 mmHg compared with proprano lol alone and by 3.7 mmHg compared with ramipril alone. Ramipril had n o effect on the bradycardia induced by propranolol. Propranolol reduce d exercise mean arterial pressure by 9 mmHg (day 4) and heart rate by 7 beats . min-1 (day 4) compared with ramipril; this was not affected by co-administration of ramipril. On day 4 the average plasma renin ac tivity was not significantly higher than after the combination. ACE ac tivity was not affected by propranolol. The pharmacokinetics of ramipr il and ramiprilat were not influenced by propranolol. The combination of ramipril and propranolol has additive pharmacodynamic effects that may be useful in the treatment of hypertension.