Biliary excretion and pharmacokinetics of cefoperazone in humans.

Six patients, 40 to 81 years of age, requiring T-tube drainage of their common bile duct, were studied to assess the biliary tract excretion and pharmacokinetics of cefoperazone. Each patient received 2.0 g of cefoperazone iv over 15 min. Cefoperazone concentrations were determined in serum, urine and bile by means of bioassay and HPLC. The results were compared with a pharmacokinetic study in healthy volunteers. The mean total recovery rate of cefoperazone in urine and bile was with bioassay: 64.5 +/- 15.3% (HPLC: 62.4 +/- 15.5%) in 24 h. 18.6 +/- 14.0% (11.5 +/- 7.1%) were found in the bile and 45.9 +/- 16.2% (50.9 +/- 19.7%) in urine. Peak bile concentrations were 3642 +/- 2975 mg/l (2259 +/- 1337 mg/l) after 2-3 h. The serum levels of cefoperazone showed a slow decrease in patients with a long terminal half life (T1/2 gamma) of 380 min from 295 +/- 90 mg/l initially to 15.9 +/- 11.3 mg/l after 12 h. In normal subjects, serum concentrations decreased much faster (T1/2 gamma = 143.5 +/- 20.0 min) from 232.8 +/- 28.6 mg/l to 1.16 +/- 0.73 mg/l after 12 h. Recovery in urine was 21.4 +/- 5.6%. Using HPLC analysis, we found cefoperazone A in small concentrations in the serum and in higher concentrations in the bile and urine of the operated patients. It is debatable whether cefoperazone A is a true metabolite in vivo or a physical degradation product.