Peritoneal absorption of cefoperazone in rats.

The peritoneal absorption of cefoperazone, administered by intraperitoneal (ip) perfusion in a large volume (100 mg/40 ml), was investigated in rats. Its pharmacokinetics was also studied after ip or intravenous (iv) injection of 100 mg/kg in two groups of rats. The peritoneal uptake after the two modes of ip administration was rapid, peaking in less than 20 minutes and the means of peak concentrations were similar. The peak remained high in the group perfused with a large volume for at least 4 hours, which was the end of sample collection. In addition, the absorption half-life and the fraction (F) reaching systemic circulation were calculated and found to be 10.0 +/- 2.5 min and 0.93, respectively. A brief distribution phase (t1/2 alpha 8.0 +/- 0.67 minutes) appeared only after the iv bolus. Otherwise the decline in serum concentration was monoexponential with half-lives of 39.0 +/- 4.0 and 63.6 +/- 7.5 min for the iv and ip injected groups, respectively. The stability of cefoperazone in plasma was also investigated in this study. It was found to be unstable at physiological pH even at -30 degrees C and the samples collected should be buffered in acidic media to optimize stability. The degradation process is likely to contribute to its elimination kinetics during in vivo administration.