Kinetics of cefsulodin in patients with renal impairment

Kinetics of cefsulodin were determined after administration of a 500-mg dose to normal subjects and patients with various degrees of renal insufficiency, including those requiring hemodialysis. Elimination kinetics were described by a two-compartment model. The steady-state volume of distribution was 0.26 liters/kg regardless of renal function. When the glomerular filtration rate (GFR) was greater than 80 ml/min, the elimination half-life (t1/2) was 1.9 hr. When the GFR ranged from 79 to 53 ml/min, t1/2 was 2.9 hr. In patients with moderate renal failure, in whom the GFR was 32-22 ml/min, t1/2 was 5.7 hr. In anuric patients, t1/2 was 13.0 hr. During hemodialysis the average plasma flow was 122 ml/min, dialyzer plasma clearance was 50.9 ml/min, concentration of drug in plasma was reduced by 60%, and t1/2 decreased to 2.1 hr. After dialysis the elimination rate appeared to return to that found in subjects not undergoing dialysis. While progressive renal failure slows the elimination of cefsulodin, there is a linear relationship between elimination of cefsulodin and GFR such that dosage nomograms can be developed. In patients undergoing hemodialysis, the maintenance dose of cefsulodin should be reduced to 10% of normal, and 60% of the dose should be given after hemodialysis.