LABORATORY EVALUATION OF CARFECILLIN, A CARBENICILLIN PHENYL ESTER

II ABSORPTION, EXCRETION AND METABOLISM

Abstract

The serum and tissue levels, and urinary, biliary and fecal excretions of carbenicillin after oral administration of carfecillin were determined in different animals. The serum levels of carbenicillin after oral administration of carfecillin 112.8 mg/kg (equivalent to 100 mg/kg of carbenicillin) were compared among Sprague-Dawley strain rats aged 4, 6 and 8 weeks. The serum levels of carbenicillin in younger male and female rats were higher than those in older rats. When the tissue levels of carfecillin given orally to rats were determined under the same conditions, carbenicillin levels in 4-week-old rats were higher in the kidneys and lungs, and were lower in the liver than those in 6-and 8-week-old rats. The authors attempted to elucidate the sites where carfecillin is hydrolyzed into carbenicillin and absorbed after oral administration to rats. In the rats with intestinal ligation, the serum levels of carbenicillin after injection of carfecillin to the upper part of the intestine were the highest and disappearance of carfecillin from this site was the most rapid.
The 24-hour urinary recovery of carbenicillin in rats aged 4, 6 and 8 weeks after oral administration of the same dose of carfecillin paralleled to the serum levels of carbenicillin. The urinary recovery in rats aged 4 weeks was twice as that in rats aged 8 weeks. About 15 percent of carbenicillin was excreted in the bile within 24 hours after oral administration of carfecillin. The disappearance rate of carfecillin in stomach was determined at the same dose to compare the disappearance of carfecillin and carbenicillin.
After oral administration of carfecillin 112. 8 mg/kg to beagle dogs carfecillin was detected in the portal vein blood but not in the femoral vein blood.
The serum levels and urinary excretion of carbenicillin in 17 healthy volunteers after oral administration of 1g carfecillin under controlled conditions were studied.