Pharmacokinetics of ketanserin in man

Kinetic data for the new antihypertensive agent ketanserin were determined in six healthy subjects after single oral (40 mg) or intravenous (0.15 mg/kg) doses. Plasma protein binding was 94.0 +/- 1.8% (mean +/- SD). Cumulative urinary excretion of unchanged drug was less than 4% within 48 h following the single dose. The maximal plasma level (Cmax) of 193 +/- 98.2 micrograms/l occurred within 0.5 to 4.0 h after oral intake. The ketanserin plasma level declined biexponentially after oral administration, and triexponentially over the 36 h following intravenous injection. The terminal elimination half-life (term. t 1/2) averaged 12.4 +/- 2.9 h and 12.8 +/- 4.8 h following oral and intravenous application, respectively. Total plasma clearance was 410 +/- 62.0 (i.v.) and 829 +/- 228 ml/min (p.o.) and the intravenous blood clearance averaged 602 +/- 91 ml/min, which indicates partly flow dependent hepatic elimination. A substantial first-pass effect led to a bioavailability of about 50% (range: 27-69%). Hepatic clearance of ketanserin followed the non-restrictive pattern. No change in blood pressure or heart rate was observed following ketanserin administration to normal volunteers.