Intraoperative ceforanide pharmacokinetics and protein binding

The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free ceforanide concentrations in the serum. A high-pressure liquid chromatography assay was used, with a centrifugal filtration system for free-drug determinations. Serum concentration data for each individual were subjected to linear regression to determine the elimination rate constants (total and free drug), volumes of distribution, and systemic clearances. The mean elimination rate constants were 0.41 and 0.50 h-1 for total and free ceforanide, respectively. The mean percentage of ceforanide bound to serum protein was 87.9%. The relationship of the free ceforanide concentration to the total concentration appeared to be linear. The data were fit to double-reciprocal and half-reciprocal relationships with good agreement, showing one binding site and an association constant range of 1.6 X 10(7) to 1.9 X 10(7) at these in vivo concentrations. The mean volume of distribution and mean systemic clearance of total drug were 100 ml/kg and 45.9 ml/min per 1.73 m2, respectively. Ceforanide consistently produced higher intraoperative total drug concentrations compared with those of cefazolin and cefoxitin from similar studies.