Ketanserin, a novel 5‐hydroxytryptamine antagonist: monotherapy in essential hypertension.

Abstract

1 Blood pressure and heart rate, supine and standing, were studied in patients with essential hypertension during 8 weeks of oral therapy with two dosage schedules of ketanserin, 40 mg once and twice daily. 2 Ketanserin caused significant reductions in both supine and standing blood pressure but no significant alterations in heart rate in both groups of patients. 3 Measurements of blood pressure and heart rate over a 24 h period during steady state conditions revealed that maximal blood pressure reduction was correlated with time to peak plasma concentrations. 4 Steady state plasma concentrations of ketanserin were significantly higher in the patients receiving 40 mg twice daily compared to 40 mg once daily. In the group with once daily treatment, tmax was 1.2 ± 0.17 h, Css 13 + 4.3 ng/ml, Cmax 137 + 19.6 ng/ml and ty,Z 9.6 + 1.27 h.

Ketanserin pharmacokinetics in patients with renal failure.

“…Ketanserinol is reported to be pharmacologically inactive Van Peer et al, 1986). Thus, side effects reported by our patients on 20 mg twice daily did not differ from those reported in otherwise healthy subjects (Hedner et al, 1983). Therefore it may be expected that the accumulation of ketanserin-ol in renal failure Most of the ketanserin present in the blood of patients with renal failure was found to be proteinbound (93.7%), the mean free fraction being 26% higher than in healthy volunteers.…”

“…Elevated free plasma concentrations of ketanserin might be associated with an increased effectiveness and with the observed adverse reactions in the patients given 40 mg twice daily. Dosages of 40 and 20 mg twice daily did not lead to elevated plasma concentrations of ketanserin as compared with those that have been reported in individuals with normal kidney function after the same dosage (Hedner et al, 1983;Kurowski, 1985;Persson etal., 1987), and 20 mg twice daily appeared to be well tolerated by our patients.…”

“…After oral administration, Wenting et al, 1984) and oral administration ketanserin is rapidly and completely absorbed. (Hedner et al, 1983;Trenk et al, 1983). Studies The absolute oral bioavailability is 50% on the pharmacokinetics and bioavailability of Reimann et al, 1983; ketanserin in young adult volunteers (Heykants Trenk et al, 1983) reflecting presystemic et al, 1986Reimann et al, 1983;Trenk et al, metabolism in the liver and involving the reduc-1983; Van Peer et al, 1986), the elderly tion of ketanserin to ketanserin-ol (Van Peer et (Kurowski, 1985), hypertensive patients (Persson al., 1986 negligible but ketanserin-ol excretion accounts for 13 to 17% of the ketanserin dose Van Peer et al, 1986).…”

Ketanserin in combination with beta‐adrenergic receptor blocking agents in the treatment of essential hypertension.

“…Regardless of the precise mechanism of action, ketanserin has a favourable haemodynamic profile. In contrast to most other vasodilating agents, the BP reduction induced by ketanserin is not associated with a compensatory increase in HR and sympathetic activity (Wenting et al, 1982;Hedner et al, 1983Hedner et al, , 1984Persson et al, 1983) or pronounced orthostatic reactions during maintenance therapy (Wenting et al, 1982Persson et al, 1983). For this reason ketanserin can be used in monotherapy (Andren et al, 1983;Hedner et al, , 1984Persson et al, 1983).…”

“…However, the compound also blocks aladrenoceptors and at least after acute administration in animals (Persson et al, 1982;Fozard, 1982, Kalkman et al, 1982 and in man (Reimann & Frolich, 1983) this action may contribute to the antihypertensive effect. When given to patients with essential hypertension, ketanserin lowers blood pressure during acute as well as chronic administration (DeCree et al, 1981;Wenting et al, 1982;Hedner et al, 1983;Persson et al, 1983), primarily by reducing peripheral vascular resistance (Demoulin et al, 1981). Ketanserin is an effective antihypertensive agent during rest as well as exercise in a majority of patients when administered as monotherapy .…”