Ceforanide pharmacokinetics in haemodialysis: The effect of ultrafiltration

Abstract

The kinetics of ceforanide in plasma and dialysate was studied in 8 patients with terminal renal impairment after undergoing haemodialysis sessions lasting between 4 and 5 h. All patients received a single i.v. dose of 15 mg kg-1 of the drug at the start of the session. The dialysers used in this study were Spiraflow capillar 1.3 m2, Travenol plates 1.4 m2, and PAN plates. Blood flow ranged between 200 and 300 ml min-1 and dialysate flow between 500-650 ml min-1. Plasma ceforanide levels were measured at the input and output of the dialyser and the antibiotic levels in dialysate were determined coinciding with the withdrawal times of the blood samples. A microbiologic plate diffusion method was used to determine the antibiotic concentrations. The mean values of some pharmacokinetic parameters of ceforanide calculated with a non-linear regression program from the data obtained from arterial blood were the following: alpha (h-1) = 4.14 +/- 1.32; beta (h-1) = 0.26 +/- 0.07; t1/2 beta (h) = 2.82 +/- 0.82; Vdss (1) = 10.24 +/- 2.14. From the relationships between the antibiotic concentrations at the input and output of the dialyser it was possible to calculate an extraction coefficient of 0.11 +/- 0.06. The dialysis clearance of ceforanide was calculated from the determination of the extraction coefficient and from the measuring of antibiotic in dialysate, though different results were obtained with the two methods. Dialysis clearance calculated from the extraction coefficient showed a mean value of 18.68 +/- 12.16 ml min-1, significantly lower (p less than 0.01) than that established by analysis of the antibiotic in dialysate, which was 41.55 +/- 15.83 ml min-1. These differences may be attributed to problems related to the determination of blood flow and to the ultrafiltration capacity of the dialysis membranes. A linear relationship was established between the percentage error in the observed and predicted extraction coefficients and the ultrafiltration rate. The results obtained suggest that the simultaneous measurement of the antibiotic in plasma and dialysate is the most suitable method for predicting the dialysis clearance of the drug. The amount of antibiotic extracted over a 4-hour dialysis session proved to be equal to 57.85 +/- 15.62 per cent of the dose administered.