Lack of effect of propranolol on the steady-state plasma levels of ketanserin.

The effect of propranolol treatment on the steady-state plasma levels of ketanserin was evaluated in 6 patients suffering from borderline hypertension and in 2 healthy volunteers. All subjects received ketanserin 40 mg b.i.d. for 21 days. From day 8 to 14 of the study propranolol was given additionally in a dose of 80 mg bid. This dose of propranolol had to be reduced in 3 subjects because of side effects. Steady-state plasma concentrations (measured 4-6 h after the dose) of ketanserin varied from 51.0 +/- 13.6 to 67.8 +/- 13.8 ng/ml (mean +/- SEM) during the entire study period. Treatment with propranolol (plasma concentrations ranged from 45.7 +/- 15.8 to 65.7 +/- 11.4 ng/ml) did not significantly alter the plasma concentrations of ketanserin. The same was true for the minimal plasma concentrations of ketanserin measured at the end of each treatment period. Blood pressure decreased during the 21 days treatment period with ketanserin (mean systolic blood pressure decreased from 144 +/- 5 to 123 +/- 7 and diastolic from 81 +/- 3 to 72 +/- 5 mmHg). Propranolol had a slight additional hypotensive effect. Heart rate decreased during treatment with propranolol. It is concluded that simultaneous oral treatment with propranolol in doses up to 160 mg/day does not alter the first-pass metabolism and the elimination kinetics of ketanserin.