Clinical Pharmacokinetics

, Volume 20, Issue 4, pp 263–279 | Cite as

Clinical Pharmacokinetics of Ketanserin

  • Bengt Persson
  • Jos Heykants
  • Thomas Hedner
Review Article Drug Disposition


Ketanserin is a serotonin S2-receptor antagonist introduced for the treatment of arterial hypertension and vasospastic disorders. Plasma concentrations of ketanserin (and some metabolites) can be measured with high performance liquid chromatography using ultraviolet or fluorescence detection, or by radioimmunoassay. The methods are sensitive, accurate and specific. Following oral administration ketanserin is almost completely (more than 98%) and rapidly absorbed and peak concentrations in plasma are reached within 0.5 to 2 hours. It is subject to considerable extraction and metabolism in the liver (first-pass effect) and the absolute bioavailability is around 50%. The compound is extensively distributed to tissues and the volume of distribution is in the order of 3 to 6 L/kg. In plasma ketanserin binds avidly to plasma proteins, mainly albumin, and the free fraction is around 5%. Ketanserin is extensively metabolised and less than 2% is excreted as the parent compound. The major metabolic pathway is by ketone reduction leading to formation of ketanserin-ol which is mainly excreted in the urine. Ketanserin-ol, which by itself does not contribute to the overall pharmacological effect, is partly reoxidised into ketanserin, and it is likely that the terminal half-life of the parent compound is related to the slow ketanserin regeneration from the metabolite.

Following intravenous administration plasma ketanserin concentrations decay triexponentially with sequential half-lives of 0.13, 2 and 14.3h. The terminal half-life is similar after oral administration. Following long term oral dosing (20 or 40mg twice daily) the pharmacokinetics remain linear and steady-state concentrations, which can be predicted from single-dose kinetics, are reached within 4 days. During long term treatment with the common dosage of 40mg twice daily, steady-state concentrations fluctuate between 40 µg/L (trough) and 100 to 140 µg/L (peak). The pharmacokinetic properties of ketanserin are predictable in a wide group of patients and there is no influence from the duration of treatment, age and sex of the patient or concomitant treatment with β-blockers or diuretics. There is no direct relationship between plasma concentrations of ketanserin and the antihypertensive effect in a group of patients. Side effects, including prolongation of the Q-T interval, are dose-dependent and, at least in the individual patient, related to peak plasma concentrations.

In separate studies the pharmacokinetics of ketanserin were investigated in special patient groups, namely the elderly and patients with hepatic and renal insufficiency. In elderly patients over 65 years of age the pharmacokinetics were similar to those found in healthy subjects; if anything, the bioavailability and area under the plasma concentration-time curve tended to be higher in some patients. In patients with severe hepatocellular insufficiency, the bioavailability of ketanserin is markedly higher due to a reduced hepatic elimination; in spite of higher plasma concentrations the terminal half-life is not changed. In view of these observations a higher dosage than 20mg twice daily is not likely to be required. In patients with renal insufficiency, elimination of the metabolite ketanserin-ol is prolonged but adaptation to lower doses of ketanserin is probably not necessary since plasma concentrations of the parent compound are similar to those seen in patients with normal kidney function.

Studies in vitro with ketanserin at concentrations normally seen in patients on long term therapy indicate that ketanserin does not displace other drugs from their protein binding sites in plasma. Conversely, the protein binding of ketanserin is not influenced by the coadministration of other highly bound drugs. There is no evidence that ketanserin induces or reduces hepatic enzyme systems, and it is therefore unlikely that ketanserin treatment will have clinically important effects on the metabolism of concurrently administered drugs, but formal interaction studies are lacking. Combined treatment with propranolol or cimetidine did not influence the pharmacokinetics of ketanserin. Furthermore, ketanserin did not appreciably alter the single-dose pharmacokinetics of digoxin and digitoxin or the steady-state concentrations of digoxin during long term therapy.


High Performance Liquid Chromatography Digoxin Clinical Pharmacology Cimetidine Clinical Pharmacokinetic 
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Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Bengt Persson
    • 1
    • 2
  • Jos Heykants
    • 1
    • 2
  • Thomas Hedner
    • 1
    • 2
  1. 1.Department of Medicine I and Clinical PharmacologySahlgren’s HospitalGothenburgSweden
  2. 2.Department of Drug Metabolism and PharmacokineticsJanssen PharmaceuticaBeerseBelgium

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