Comparative in vivo activity of bacampicillin and amoxycillin.

Bacampicillin is an orally well-absorbed pro-drug of ampicillin giving high in vivo levels of the latter. Its therapeutic activity was compared with that of amoxycillin in two experimental infection models in mice. The animals were infected with suspensions of Escherichia coli III and Haemophilus influenzae 22863 intraperitoneally and treated orally four hours afterwards with one of the two compounds. The antibacterial activity of the compounds was determined as CD50 values or by making viable counts in the blood and in organ homogenates of the animals. Ampicillin and amoxycillin had the same inhibitory but different bactericidal activity against the test strains. Both compounds appeared to have similar therapeutic activity and were found to cause a rapid decrease of the bacterial counts in the animals. Bacampicillin appeared to give a more rapid bactericidal activity than amoxycillin against the Haemophilus influenzae strain, whereas amoxycillin initially appeared more bactericidal against the Escherichia coli infection.

Evaluation of amino penicillins in experimental infections in mice.

The therapeutic activity of bacampicillin compared to that of ampicillin and amoxycillin was evaluated against experimental infections in mice. Median curative doses (CD50) were determined in groups of animals challenged with bacterial suspensions injected intraperitoneally together with mucin and treated orally with the penicillins. When treated directly after the infection bacampicillin was slightly more active than ampicillin, whereas it was significantly more active than ampicillin and at least as active as amoxycillin when the treatment was instituted not until four hours after infection. Bacterial counts made on various organ homogenates from infected animals four hours after the infection showed that a generalized infection with high bacterial concentrations had developed. Penicillin administration caused a significant reduction in the bacterial counts and the bactericidal activity in vivo obtained after administration of bacampicillin appeared as good as that of amoxycillin.

Bacampicillin: a new orally well-absorbed derivative of ampicillin.

Bacampicillin (proposed international nonproprietary name), 1'-ethoxycarbonyloxyethyl 6-(d-alpha-aminophenylacetamido)penicillanate, is a new orally well-absorbed penicillin, highly active in vivo due to rapid transformation into ampicillin. The compound is stable in vitro at gastric pH and hydrolyzed slowly to ampicillin at neutral pH but very rapidly in the presence of biological fluids, e.g., tissue homogenates or serum. In vivo the transformation into ampicillin is so rapid that no unchanged compound could be detected in the blood after oral administration of bacampicillin to rats, dogs, and humans. On oral administration to mice, rats, and dogs, bacampicillin was found to be better absorbed than ampicillin, giving higher and earlier peak blood levels of ampicillin. The bioavailability of bacampicillin in rats and dogs was three to four times higher than that of an equimolar amount of ampicillin. On oral administration to rats, bacampicillin was found to give higher levels of ampicillin in organs such as the kidney, liver, and spleen than ampicillin itself. In "tissue cages" in rats, higher transudate levels of antibiotic were found after oral administration of bacampicillin than after ampicillin. On oral treatment of experimentally infected mice, bacampicillin was found to be more active than ampicillin.