[Pharmacokinetic study of a cephalosporin: cefoperazone in patients with a Kehr drain].

Cefoperazone is a semi-synthetic cefalosporine for parenteral use which has an excellent activity against a wide range of grampositive and gramnegative bacteria, especially Pseudomonas aeruginosa, Enterobacter, Proteus indole positive and Serratia marcescens. The pharmacokinetics of the new antibiotic have been studied in patients who had undergone cholecystectomy and choledochotomy for lithiasis and who required T-tube drainage of the bile duct. Five patients were anicteric and one was icteric. Mean serum concentration of cefoperazone determined by a microbiological method) measured after a two-hour intravenous perfusion of 2 g cefoperazone was 198.6 microgram/lm; this level is higher than the mean level measured in normal subjects (134 microgram/ml) but lower than the mean level measured in patients with hepatic insufficiency (208 microgram/ml). Apparent half life of elimination was longer (mean 4.1 hours) in the patients than in controls (mean 1.6 hours) and compares with that of patients with hepatic insufficiency (mean 4.3 hours). The distribution volume and renal clearance are similar to that in healthy volunteers and patients with hepatic insufficiency. Extrarenal clearance of cefoperazone was significantly lower in our patients (15.8 ml/min), as it is in patients with hepatic insufficiency (7.3 ml/min), than in the control group (59.4) ml/min). Cefoperazone concentrations in the bile were 10-20 times higher than those in the serum; in the icteric patient the concentrations achieved were still higher than the MIC values for organisms commonly encountered in the bile. These results open the way to the use of cefoperazone to treat infectious biliary diseases, particularly angiocholitis, which need a high biliary antibiotic concentration.