Determination of elimination of pefloxacin and of its derivatives in continuous hemodiafiltration

Continuous venovenous hemofiltration with dialysis (CVVHD) is being increasingly used to treat acute renal failure. However, because of the-lack of data on the clearance of therapeutic agents during this treatment, there is a risk of using inappropriate dosages. This in vitro study was undertaken to determine the clearance of pefloxacin (P) and its two main metabolites (active N-desmethyl P and inactive N-oxide P) during CVVHD. Acitrate-dextrose (ACD) anticoagulated fresh human blood containing P and its two metabolites in the usual therapeutic levels was circulated at a rate of 100 ml min.-1 through a closed-circuit continuous venovenous hemofiltration with dialysis unit (BSM 22-Hospal hemofilter). Temperature and ionic composition of the blood were controlled. Dialysate (L2D, Hospal) was circulated on the other side of the continuous venovenous hemofiltration with dialysis membrane at three different flow rates (Qdi) (0, 500 and 1,000 ml.h-1. The dialysate/ultrafiltrate outflow was adjusted using a withdrawal pump to obtain nul ultrafiltration. Arterial blood, venous blood and ultrafiltrate were sampled simultaneously at different time points for High Performance Liquid Chromatography (HPLC) assays and determination of the clearances (Cl) and sieving coefficients (s) of each compound. Pefloxacin had a sieving coefficient of 0.42 and a clearance of 6.8 ml min-1 when Qdi was nul. With the blood flow used, clearances were found to be correlated with the dialysate flow rate; when this rate was 500 ml h-1, a pefloxacin clearance similar to that seen in healthy subjects was obtained (15.2 ml min-1). The two bacteriologically active forms of the drug (pefloxacin and N-desmethyl P) had similar elimination parameters.(ABSTRACT TRUNCATED AT 250 WORDS)