Blood pressure reduction and pharmacokinetics of ketanserin in hypertensive patients.

Pharmacokinetic and antihypertensive effects of the S2-serotonergic antagonist ketanserin were determined in 10 patients with essential hypertension (WHO stages I-II) after a single intravenous (0.15 mg/kg) and a single oral (40 mg) dose as well as during steady-state conditions on 40 mg once-daily dose regimen. The maximal plasma concentration (Cmax) of 99 +/- 14 and 97 +/- 14 ng/ml occurred approximately 1 h after single oral and chronic oral intake, respectively. The minimum steady-state concentration (Cssmin) was 13 +/- 2 ng/ml on a 40 mg once-daily regimen. Terminal half-lives (T1/2 beta) were 6.5 +/- 0.4 and 9.0 +/- 0.9 h after intravenous and single oral administration. During steady-state therapy the elimination half-life (24.7 +/- 2.6 h) was significantly increased compared to single dose administration. Bioavailability ranged between 15 and 60%, indicating a substantial first-pass effect. After intravenous ketanserin, mean supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) were maximally reduced after 30 min. A single oral 40 mg dose reduced mean supine SBP/DBP by 31 +/- 8/16 +/- 5 (P less than 0.01/P less than 0.05) at maximal plasma ketanserin concentrations. The SBP and DBP were reduced over 24 h during steady-state conditions on 40 mg once-daily treatment and the mean supine blood pressure reduction 24 h after dose intake was 23 +/- 7/16 +/- 4 mmHg compared to placebo control (P less than 0.05/P less than 0.01). The data from this study indicate that ketanserin monotherapy may lower blood pressure over 24 h in a once-daily regimen.