Pharmacokinetics of ceftazidime in normal and uremic subjects

Abstract

The pharmacokinetics of ceftazidime [an antibacterial agent], administered as a single i.v. dose of 15 mg/kg given in a bolus injection over 3 min, were investigated in 5 normal subjects and in 19 uremic patients. The subjects studied were divided into 5 groups according to values for endogenous creatinine clearance (CLCR): group 1, 5 subjects with CLCR > 80 ml/min; group 2, 5 patients with CLCR = 30-80 ml/min; group 3, 6 patients with CLCR = 10-30 ml/min; group 4, 4 patients with CLCR = 2-10 ml/min; and group 5, 4 anuric patients on hemodialysis. A 2-compartment open model was used to calculate the pharmacokinetic parameters. In normal subjects, the mean apparent elimination half-life was 1.57 .+-. 0.13 h. The central distribution volume and the apparent volume of distribution were 0.127 .+-. 0.023 and 0.230 .+-. 0.015 l/kg, respectively. Of the injected dose, 83.6 .+-. 3.6% was eliminated in the urine as parent drug within 24 h. The terminal half-life increased with impairment of renal function to .apprx. 25 h in severely uremic patients. Impairment of function did not significantly modify the half-life at .alpha. phase, central distribution volume or apparent distribution volume. A 6-8 h hemodialysis procedure reduced concentrations of ceftazidime in plasma by .apprx. 88%; the elimination half-life was 2.8 .+-. 0.2 h. There was no evidence of accumulation of ceftazidime in 4 patients with severe and chronic impariment of function who received doses of 0.5-1.0 g every 24 h for 10 days.