Journal of Antimicrobial Chemotherapy (1986) 18, 203-211
© 1986 The British Society for Antimicrobial Chemotherapy
research-article |
Pharmacokinetics of cefonicid in uraemic patients
aU.E.R. Medecine Rouen bC.E.R.O.M. Poitiers France
accepted 2 December 1985
Reprints requests to: Professor J. P. Fillastre, Hópital de Bois-Guillaume, 76230 Boisguillaume, France.
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 gcefonicid, as a bolus injection. Five groups of subjects were studied: group I, GFR > 80 ml/min, group II 30 < GFR < 80 ml/min, group III 10 < GFR < 30 ml/min, group IV GFR 
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/1 and the apparent volume of distribution was 0.18–0.201/kg for all patients. The elimination half-life (T
ß) 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 1) to 1.9±0.2ml/min/1.73m2 (group V). Renal clearance fell from 19.0±4.9ml/min/ 1.73 m2 (group I) to 1.0±0.4ml/min/1.73m2 (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.