Use of in vitro models of haemofiltration and haemodiafiltration to estimate dosage regimens for critically ill patients prescribed cefpirome.
BACKGROUND
The physico-chemical properties of cefpirome (low protein binding, high water solubility and low molecular weight) suggest that it may be lost readily from the extracorporeal circulation of intensive care unit patients during continuous renal replacement therapy.


METHODS
In order to make informed dosage recommendations for patients receiving artificial renal support, cefpirome loss from human blood has been quantified using in vitro models of continuous haemofiltration and haemodiafiltration. Cefpirome clearance was measured using three membrane types at varying ultrafiltrate (UFR) and dialysis flow rates (Qd).


RESULTS
During haemofiltration cefpirome was found to cross hollow fibre polyamide (PA) and polyacrylonitrile (PAN) membranes with equal efficiency. The mean sieving coefficients (S) of both PA and PAN membranes were consistently high (> 0.7) when two different ultrafiltration rates were used. Changing the ultrafiltration rate or membrane type had no significant effect on the sieving coefficient of cefpirome but did result in an increase in cefpirome filter clearance (Fcl). Using the haemodiafiltration model, cefpirome penetrated PAN membranes (flat plate AN69S) more efficiently than hollow fibre PA membranes (FH66D). In each case, increasing the dialysis flow rate reduced the S-value. However, although increasing Qd was associated with a greater Fcl of cefpirome when PAN membranes were employed, no such relationship was found for the PA hollow fibre membrane.


CONCLUSIONS
The information generated can be used to estimate a dosing regimen for intensive care patients prescribed cefpirome and receiving continuous renal replacement therapy.
Phillips
G J
GJ
School of Pharmacy and Biomolecular Sciences, Faculty of Science and Engineering, University of Brighton, Moulsecoomb, UK.
Davies
J G
JG
Olliff
C J
CJ
Kingswood
C
C
Street
M
M
D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness / Q000628:therapy*; D017583:Hemodiafiltration / Q000379:methods; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D008954:Models, Biological; D017582:Renal Replacement Therapy / Q000379:methods / Q000592:standards*; D000097572:Cefpirome
D002511:Cephalosporins; D008567:Membranes, Artificial; D000097572:Cefpirome