Experimental and clinical evaluation of the biliary pharmacokinetic profile of cefpiramide, a new cephalosporin with high hepatic elimination.

Biliary elimination of cefpiramide was studied experimentally and in human subjects using chromatography (HPLC). During a 3-h perfusion of five isolated rabbit liver preparations, 40.4% of cefpiramide added to the circulating blood was eliminated in the bile and only 0.3% was metabolized in the liver. In five healthy subjects, after a single intravenous administration of 1 g of cefpiramide, a maximal concentration of 339 +/- 107 micrograms/ml was reached during the 2nd hour in the collected duodenal fluid, and 1.23 +/- 0.20% of the given dose was recovered within 4 h. In ten cholecystectomized patients provided with a T-tube, intravenous injection of 1 g of cefpiramide resulted during the 2nd hour in a biliary peak concentration of 1161 +/- 392 micrograms/ml. The total amount of antibiotic eliminated in the bile over 24 h averaged 231.5 +/- 39.1 mg, corresponding to 23.2 +/- 3.9% of the administered dose. Hepatic clearance was 3.13 ml/h. Intraoperative specimens sampled simultaneously 1 h after intravenous administration of 1 g of the antibiotic in ten patients undergoing cholecystectomy showed cefpiramide concentrations of 157 +/- 21 micrograms/ml in serum, 1726 +/- 501 micrograms/ml in choledocal bile, 84 +/- 33 micrograms/ml in gall-bladder bile and 22.6 +/- 4.2 micrograms/g in gall-bladder wall. These data emphasize the excellent biliary tropism of cefpiramide, and compare favourably with results concerning 19 other beta-lactams previously studied under the same conditions. They constitute a good prerequisite for possible beneficial treatment of biliary tract infections.