The availability of carfecillin and its phenol moiety in rat and dog.

1. Studies have shown that hydrolysis of carfecillin to carbenicillin and phenol in vitro occurs in blood, liver and gut tissues of rat and dog. Extremely rapid hydrolysis was observed in the blood and liver of the rat. 2. Absorption studies in intestinally-perfused rats showed that following administration of either [14C]phenol or [phenol-14C]carfecillin, the half-life values of radioactivity in the intestinal lumen were 6 min and 47 min respectively. 3. Following oral administration of phenol to rats and dogs at 300 mg/kg and 40 mg/kg respectively, maximum plasma concn. of phenol were 26 microgram/ml. However, following oral administration of carfecillin to rats and dogs at dose levels of 3000 and 800 mg/kg respectively, no significant amounts of free phenol or intact carfecillin were detected (< 1 microgram/ml). The very low concentrations of phenol found after carfecillin administration and the concomitant absence of acute phenol toxicity is explained by the slow absorption of carfecillin and its slow hydrolysis to phenol in the gut lumen. 4. In the dog, phenol which enters the portal circulation as carfecillin appears to undergo significant 'first pass' metabolism by the liver, while no such effect was observed if free phenol was administered.

Carfecillin: antibacterial activity in vitro and in vivo.

Carfecillin, the alpha-phenyl ester of carbenicillin, hydrolyses rapidly in the presence of serum or body tissues to liberate carbenicillin but hydrolysis is less rapid in aqueous solution. The activity of carfecillin in antibacterial tests in vitro depends upon the extent of hydrolysis to carbenicillin, and in conventional serial dilution tests carfecillin shows an antibacterial spectrum generally similar to that of carbenicillin due to extensive hydrolysis. However, in tests in which the extent of hydrolysis is reduced, carfecillin displays lesser activity than carbenicillin against gram-negative bacilli and greater activity against gram-positive cocci. In the presence of serum carfecillin is hydrolysed rapidly to carbenicillin and the activity shown is solely that of carbenicillin. Unlike carbenicillin, carfecillin is well absorbed in mice after oral administration, producing significant carbenicillin blood concentrations and the compound is as effective by the oral route in the treatment of various experimental mouse infections as is parenteral carbenicillin.