cefamandole and Uremia

Eight subjects with normal renal function and 20 uraemic patients with various degrees of renal insufficiency were given a single iv dose of 1.0 g cefonicid, as a bolus injection. Five groups of subjects were studied: group I, GFR greater than 80 ml/min, group II 30 less than GFR less than 80 ml/min, group III 10 less than GFR less than 30 ml/min, group IV GFR less than or equal to 10 ml/min and group V, haemodialysis patients. Cefonicid concentrations in plasma and urine were measured by microbiological assay (MA) and HPLC method. Results were similar with the two techniques. The mean peak plasma levels were 200-300 mg/l and the apparent volume of distribution was 0.18-0.20 1/kg for all patients. The elimination half-life (T 1(2) beta) increased as renal function decreased: 5.31 +/- 1.30 h in healthy subjects and 58.92 +/- 12.38 h in patients with end-stage renal disease. Urinary elimination of cefonicid was inversely related to the degree of renal impairment: 83% of the dose in 24 h in normal subjects and 13.6% of the dose in patients with severe renal failure. Total body clearance decreased from 23.9 +/- 3.4 ml/min/1.73 m2 (group I) to 1.9 +/- 0.2 ml/min/1.73 m2 (group V). Renal clearance fell from 19.0 +/- 4.9 ml/min/1.73 m2 (group I) to 1.0 +/- 0.4 ml/min/1.73 m2 (group IV). The fractional clearance and the non renal clearance were similar in normal subjects and in uraemic patients. Cefonicid is not haemodializable because of its high protein binding. Dosage of cefonicid should be adjusted according to the degree of renal impairment. Supplemental doses are not necessary after haemodialysis.

Topics: Adult; Aged; Cefamandole; Cefonicid; Creatinine; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Uremia

A single intravenous 15 mg/kg dose of cefamandole was given to 6 patients in chronic renal failure before hemodialysis, and 3 were examined during an interdialysis period. Mean cefamandole clearance by hemodialysis was 24 +/- 12 ml/min; 35 +/- 15% of the dose was recovered in the dialysate. The cefamandole half-life (1 1/2) on dialysis was 4.0 +/- 0.29 hr; off dialysis it was 13.9 +/- 4.2 hr. High urine concentrations of cefamandole in these patients suggests usefulness in urinary tract infection.

Topics: Adult; Cefamandole; Cephalosporins; Creatinine; Female; Hematocrit; Humans; Kinetics; Male; Middle Aged; Renal Dialysis; Uremia

Platelet function and coagulation were tested after brief in vivo exposure to cefamandole nafate and in the presence of various concentrations of the drug in vitro. Alterations in hemostatic function were observed only with exposure to drug concentrations severalfold higher than those expected to prevail clinically.

Topics: Adenosine Diphosphate; Blood Coagulation; Blood Platelets; Cefamandole; Cephalosporins; Collagen; Epinephrine; Humans; Penicillin G; Platelet Aggregation; Ristocetin; Time Factors; Uremia