RESUMO
Ten healthy volunteers received a single 10 mg intravenous dose of the 5-hydroxytryptamine-2 serotonin antagonist ketanserin in the control state and again during coadministration of propranolol, 80 mg b.i.d. There were no differences between control and propranolol treatment conditions in ketanserin volume of distribution (5.2 vs. 3.8 L/kg), elimination half-life (6.6 vs. 4.7 hours), clearance (9.7 vs. 10.0 ml/min/kg), or 72-hour excretion of intact ketanserin (0.7% vs. 0.7% of dose) or ketanserinol (21.8% vs. 24.9% of dose). In a second study, eight volunteers received a 160 mg oral dose of propranolol hydrochloride in the control state and again during treatment with ketanserin, 40 mg b.i.d. There were no significant differences between control and ketanserin conditions in the time of peak serum propranolol concentration (2.1 vs. 1.5 hours after dosage) or elimination half-life (3.8 vs. 4.1 hours). However, ketanserin increased peak serum propranolol concentrations (169 vs. 233 ng/ml) and reduced oral clearance (39 vs. 27 ml/min/kg); the differences were not statistically significant (0.05 less than P less than 0.1) with a sample size of eight. Thus therapeutic doses of propranolol in healthy volunteers do not alter the kinetics of a single dose of ketanserin. Therapeutic doses of ketanserin may impair oral clearance of propranolol, leading to increased area under the serum concentration curve and higher peak serum levels.
