Pharmacokinetics of Cefuroxime and Ceftazidime in Patients with Acute Renal Failure Treated by Continuous Arteriovenous Haemodialysis

Abstract

To determine appropriate doses of cefuroxime and ceftazidime for septic patients with acute renal failure (ARF) treated by continuous arteriovenous haemodialysis (CAVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received cefuroxime 500 mg (n = 11) or 750 mg (n = 1), or ceftazidime 500 mg (n = 9) i.v. 12-hourly and all studies were done at steady-state. For cefuroxime, volume of distribution (Vdarea) was 22.8 +/- 3.5 l, terminal elimination half-life (t1/2) 12.6 +/- 2.2 h and total body clearance (TBC) 22.3 +/- 3.0 ml/min (mean +/- SEM). Mean sieving coefficient (SC) was 0.90 +/- 0.12 and filter clearances at Qd 1 and 2 l/h were 14.0 +/- 2.3 and 16.2 +/- 3.4 ml/min respectively. For ceftazidime, Vdarea was 31.1 +/- 6.5 l, t1/2 14.7 +/- 3.3 h, and TBC 24.8 +/- 0.8 ml/min. Mean SC was 0.86 +/- 0.03, and filter clearances at Qd 1 and 2 l/h 13.1 +/- 1.2 and 15.2 +/- 1.5 ml/min. Satisfactory plasma concentrations of both antibiotics were maintained in all patients during treatment. These data suggest that cefuroxime 500-750 mg and ceftazidime 500 mg 12-hourly are suitable doses for patients with ARF treated by CAVHD.

Determinants of Ceftazidime Clearance by Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodialysis

“…Since net Q UF ranged from 3.0 to 9.2% of nominal Q DI during the CVVHD segment of this study, the observed ceftazidime clearances predominantly reflect the effects of alterations in blood and dialysate flow on diffusion across the membrane. Unfortunately, the previously published studies of ceftazidime clearance during CVVHD did not control ultrafiltration rate to this degree, and thus their results cannot be directly compared to our observations (6,27). Furthermore, ceftazidime clearance by CVVHD has been previously evaluated with only the AN69 filter.…”

“…The disposition of ceftazidime (6,12,27) during CVVH has been reported in single case reports or as a series of clinical cases. Unfortunately, it is difficult, if not impossible, to control the critical variables that may affect the clearance of ceftazidime in acutely ill patients.…”

“…These included a 0. 6 CRRT procedure. Venous access was obtained by cannulation of the patient's hemodialysis arteriovenous fistula or polytetrafluoroethylene graft.…”

“…Thus, the half-life of ceftazidime increases significantly in patients with renal insufficiency (2). The reported clearance of ceftazidime during CVVH, CVVHD, or CVVHDF or their arterial derivatives ranges from 4.2 to 24.0 ml/min (3,6,12,13,27). The methods utilized to determine the clearance of ceftazidime, however, were often not provided or consisted of multiple assumptions (e.g., normal degree of protein binding and consistency of blood, dialysate, and ultrafiltrate flow rates).…”

In vitro AN69 and Polysulphone Membrane Permeability to Ceftazidime and in vivo Pharmacokinetics during Continuous Renal Replacement Therapies

“…There are some clinical data on the removal of ceftazidime by CRRT [2,[11][12][13][14][15] , but it is difficult to compare data from different forms of CRRT because the mechanism of drug removal in hemofiltration (i.e., drug removal by convection) differs from that of hemodiafiltration (i.e., removal by convection plus diffusion) [16] . There are also differences in flow rates, dose regimens and membranes used in the studies mentioned above.…”