Ketanserin pharmacokinetics in patients with renal failure.

1. The pharmacokinetics of ketanserin and its major metabolite ketanserin-ol were investigated after a single oral dose of 40 mg and after chronic oral administration of 20 or 40 mg twice daily for 10 days in 12 patients with chronic renal insufficiency of whom six were on intermittent haemodialysis. Plasma protein binding of ketanserin was measured in these 12 patients and in eight healthy volunteers. 2. In both dialysis and non-dialysis patients the terminal half-life of ketanserin (mean +/- s.d.) was prolonged compared with that reported previously for healthy volunteers (28 +/- 4 h vs 18 +/- 4 h). This may be explained by a lowered renal clearance of ketanserin-ol from which ketanserin is partly regenerated. 3. In patients with chronic renal insufficiency plasma ketanserin concentrations were similar to those found in healthy subjects after the same dose. Plasma ketanserin-ol concentrations were elevated, resulting in a raised AUC ratio of ketanserin-ol to ketanserin as compared with healthy individuals (7.3 +/- 4.0 vs 3.2 +/- 0.7). 4. Urinary excretion of ketanserin was negligible in both dialysis and non-dialysis patients, and ketanserin-ol excretion was markedly lowered. 5. The plasma protein binding of ketanserin was slightly reduced in comparison with healthy volunteers (93.7 +/- 1.0% vs 95.0 +/- 0.2%). 6. A dose regimen of 20 mg twice daily appeared to be well tolerated in spite of less plasma binding in renal failure.