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

Abstract

Background: Ceftazidime is a third-generation cephalosporin almost entirely eliminated by glomerular filtration and dose reductions are essential in patients with renal impairment. The physicochemical and pharmacokinetic properties of ceftazidime make it susceptible to be eliminated by continuous renal replacement therapies (CRRT), but there is little clinical information to guide the correct administration in patients undergoing these techniques. Methods: In vitro procedures were carried out in three different fluids, using AN69 or polysulphone membranes. Four patients entered the in vivo study. Two patients received 1,000 mg every 6 h and the other two 2,000 mg every 6 h. Concentrations of ceftazidime were measured by high-performance liquid chromatography. Results: No differences were detected in thesieving coefficients (Sc) or saturation coefficients (Sa)between membranes during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHD). Sc-Sa values were close to 1 when Ringer’s lactate was used as ceftazidime vehicle, but were lower in plasma samples (p < 0.05). In patients, the Sc-Sa was 0.93 ± 0.06 and correlated well with the unbound fraction (0.86 ± 0.08). The contribution of CRRT to ceftazidime clearance was higher in anuric patients than in nonanuric patients. Conclusions: No differences were shown in vitro in the Sc obtained with both membranes during CVVH or the Sa obtained during CVVHD. The contribution of clearance by CRRT to total clearance is clearly dependent on the renal function. The administration of ceftazidime every 6 h could be associated with unnecessarily high trough levels which increase the risk of drug nephrotoxicity. Nonanuric patients undergoing CRRT need higher ceftazidime doses to reach adequate plasma concentrations against pathogens isolated in the critically ill.

Pharmacokinetics and Dialytic Clearance of Ceftazidime-Avibactam in a Critically Ill Patient on Continuous Venovenous Hemofiltration

“…The plasma pharmacokinetic parameters and dialytic clearance of ceftazidime described in this case are comparable to those previously reported in patients undergoing CVVH (8,9). There are no published data on the removal of avibactam by CVVH or on its effect on the systemic pharmacokinetics.…”

Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

“…CL CHDF,vivo Observed was estimated by Bayesian estimation using VCM-TDMEX software version 2.0 (Shionogi, Osaka, Japan) for VAN and Tagocid TDM software version 1.1 (Astellas, Osaka, Japan) for TEC. The population pharmacokinetic parameters (i.e., distribution volume of central compartment [V c ] and rate constants for the transfer from the central compartment to the peripheral compartment and for the opposite direction [k 12 and k 21 , respectively]) of VAN and TEC are summarized in Table 2 (29,33). To conduct the Bayesian estimation for VAN and TEC, CL CR was calculated using the Cockcroft-Gault equation and S cr at the final time point (11).…”

“…Several methods have been applied for the description of CHDF clearance (CL CHDF ); the simplest method, which describes CL CHDF as a product, S d ϫ Q outflow , where Q outflow represents the sum of Q D and Q F (21), is frequently applied. This method seems suitable for the prediction of pharmacokinetic properties of drugs if the S d values during CHDF are determined based on f P , as in the cases of CHF and CHD.…”

Comparison of High Performance Liquid Chromatography and Three Titrimetric Methods for the Determination of Ceftazidime in Pharmaceutical Formulations

“…The chemical structure of ceftazidime is represented by Figure 1. Ceftazidime is administrated by injection as the sodium salt or in solution with arginine and is widely distributed in body tissues and fluids; it crosses the placenta and is distributed into breast milk [15]. Penetration into the aqueous humor of the eye is relatively good after systemic administration of ceftazidime [1,16,17].…”

“…Penetration into the aqueous humor of the eye is relatively good after systemic administration of ceftazidime [1,16,17]. There is some evidence that concentrations sufficient for therapy of ocular infections due to gram-positive and certain gram-negative microorganisms can be achieved after systemic administration [15]. For Several analytical procedures are available in the literature for the analysis of cephalosporins.…”