The antihypertensive efficacy and pharmacokinetics of a single 1 mg oral dose of doxazosin were investigated in five healthy male volunteers, six patients with renal failure not on hemodialysis, and four patients with end-stage renal failure studied between two hemodialyses. The dialyzability of doxazosin was studied in five patients. The maximum fall in blood pressure of both volunteers and patients occurred between 4 and 8 hours. In four of five volunteers the blood pressure had returned to baseline within 10 to 12 hours, whereas in the patients with renal failure it took as long as 72 hours. Maximum plasma concentrations were reached in 2.6 to 3.6 hours. The mean AUC did not differ significantly between the groups. The mean (SE) elimination t1/2 was 12.6 hours (3.3) in the volunteers and 13.3 hours (1.8) in the patients with renal insufficiency (not significant). Doxazosin was not appreciably dialyzable.
The single-dose pharmacokinetics of intravenously and orally administered tinidazole were studied in normal subjects and patients with severe chronic renal failure. The clearance of tinidazole was also measured in patients on regular haemodialysis. After intravenous administration the mean elimination half-life of tinidazole was 17.1 +/- 2.3 (SD) hours in the normal subjects and 16.9 +/- 4.9 hours in patients with renal failure; the mean apparent volumes of distribution were 0.80 +/- 0.09 L/kg and 0.69 +/- 0.09 L/kg, respectively. Following oral administration the mean elimination half-life was 15.6 +/- 1.6 hours in the normal subjects and 18.4 +/- 3.5 hours in patients with renal failure; there were no statistically significant differences in these pharmacokinetic parameters. There was no accumulation of the major metabolite (hydroxymethyl tinidazole) in normal subjects or in patients with renal failure. Tinidazole clearance during haemodialysis was 71 +/- 7.7 ml/min. In the presence of renal failure no modification of tinidazole dosage would appear to be necessary. Tinidazole should be administered in full dosage following haemodialysis.
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