Cefamandole Pharmacokinetics and Dosage Adjustments in Relation to Renal Function

Abstract
The pharmacokinetic characteristics of cefamandole [a cephalosporin antibiotic active against Proteus sp., Enterobacter sp., Serratia and Escherichia coli] were determined after i.v. administration of a 1 g dose to 10 subjects with normal renal function, 10 patients with stabilized renal failure and 5 chronic nephritic patients included in an intermittent hemodialysis program. In normal subjects, biological half-life (t1/2) averaged 0.94 h, the overall elimination rate constant (Ke) was 0.7378 (h-1), total clearance was 223 ml/min per 1.73 m2 renal clearance (Cr) was 164 ml/min per 1.73 m2 and urine recovery of cefamandole over the 6 h after a dose amounted to 74% of the administered dose. In patients with stabilized renal failure and in patients on hemodialysis, t1/2 was markedly increased, with a theoretical value of 10.4 h in case of a creatinine clearance of 0. The amount of antibiotic extracted over a 6 h dialysis period accounted for 29% of the cefamandole present in the vascular compartment at the beginning of the dialysis procedure. A significant correlation was established between the values of Ke and creatinine clearances, Ccr: Ke = 0.0289 + 0.0063Ccr (r [correlation coefficient] = 0.937). This relationship was used to calculate the loading dose, maintenance doses and dosage intervals with regard to renal function. From these data recommendations regarding the adjustment of cefamandole dosage to the renal status can be made.