Pharmacokinetics and Pharmacodynamics of the 5-HT2 Receptor Antagonist Ketanserin in Man

Abstract

We determined the pharmacokinetics of ketanserin and its effects on blood pressure and heart rate in eight healthy volunteers following single-dose intravenous (10 mg) and oral (20 mg) administration of ketanserin. Following intravenous injection, plasma concentration-time data could most adequately be described by an open, three-compartment model. Plasma concentration declined with a mean terminal half-life of 15.6 +/- 6.2 h (mean +/- SD). Total clearance and volume of distribution at steady state were 0.39 +/- 0.07 L/kg/h and 3.3 +/- 1.1L/kg, respectively. The free fraction in plasma determined by equilibrium dialysis was 9.36 +/- 0.56%. Following single oral doses, a bioavailability of 0.51 +/- 0.06 was estimated. The half-life of the elimination phase tended to be somewhat longer (18.5 +/- 5.1 h, p greater than 0.05) than after intravenous administration. In addition, pharmacokinetics and effects of ketanserin on blood pressure and heart rate were investigated in two healthy volunteers after continuous treatment with ketanserin (20 mg three times a day) over a period of 5 days. No evidence of time-dependent nonlinear changes in pharmacokinetics was observed. Following single-dose as well as continuous treatment with ketanserin, no significant changes either in systolic and diastolic blood pressure or in pulse rate could be detected.