Effects of gender on propranolol pharmacok1netics and pharmacodynamics

We conducted a randomized clinical trial to test the effects of gender and menstrual cycle on the pharmacokinetics and pharmacodynamics of propranolol. Eight healthy, female volunteers were studied on 6 occasions over two menstrual cycles. Each subject took a single 60 mg dose of propranolol on 3 occasions and then blood was drawn for the determination of S- and R-propranolol concentrations at set times over the subsequent 12 hours. An isoproterenol sensitivity test was conducted at the time of each blood draw and the maximal exercise heart rate was determined before and four hours after the dose. Eight healthy male volunteers underwent exactly the same protocol. The clearance of the active S-propranolol enantiomer was less in women (21.1±1.6ml/kg/min) than in men (28.4±2.1ml/kg/min)(p < 0.05). The relationship between Spropranolol concentrations and the isoprotereno! dose required to raise the heart rate 25 beats (CD₂₅) in women was not different from that in men. The relationship between S-propranolol concentrations and the maximal exercise heart rate 4 hours after the dose in women was not different from that in men. Gender-related changes in propranolol pharmacokinetics do not seem to result in different chronotropic pharmacodynamics in men and women.