Biliary secretion of cefoperazone and its inter-relationship with bile acid transport in the rat.

Cefoperazone is a third generation cephalosporin which is secreted predominantly in bile. This study set out to examine the effect of stimulating bile choleresis on the biliary secretion of cefoperazone. Stimulation of both bile acid-dependent and independent bile flow (phenobarbitone pretreatment) hastened the peak appearance of a pulse of cefoperazone into bile. Although the biliary secretion rate of cefoperazone was enhanced by bile acid infusion, the % recovery and maximal biliary concentration were reduced. The reciprocal effect of continuous cefoperazone infusion on the rate of biliary transport of a pulse of bile acid was examined. Cefoperazone infusion hastened the biliary transport of glycocholate. Net recovery of glycocholate was unaffected.

Pharmacokinetics and effect on blood pressure of doxazosin in normal subjects and patients with renal failure.

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.