PRELIMINARY MICROBIOLOGICAL AND PHARMACOLOGICAL EVALUATION OF 6-(R-a-AMINO-3-THIENYLACETAMIDO) PENICILLANIC ACID (BL-P 875)

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BL-P 875, a new semisynthetic penicillin, was found to possess broadspectrum antibacterial activity. Its inhibitory potency for both gram-negative and gram-positive organisms was comparable in all respects to that of ampicillin. Despite this, BL-P 875 proved to be significantly more active than ampicillin when administered by the oral route in a number of experimental bacterial infections of the mouse. Median curative doses (CD₅₀) of BL-P 875 in infections produced by Streptococcus pyogenes, Klebsiella pneumoniae, Proteus mirabilis, and 1 of 2 Escherichia coli strains were less than one-half those of ampicillin. On the other hand, comparable doses were required for curing mice challenged with Staphylococcus aureus, Diplococcus pneumoniae, or Salmonella enteritidis.
Since no differences in acid stability, bactericidal effect, or serum binding were found for the 2 compounds, the probable explanation for BL-P 875's superior therapeutic activity is its higher degree of oral absorbability. BL-P 875 concentrations in mouse blood after oral administration were significantly higher (about 2-fold) than those of ampicillin at both one-half and 1 hour post-administration. Greater absorbability was also found in rats, where about twice as much BL-P 875 as ampicillin was recovered from urine after administration of a single oral dose. No differences in mouse blood levels or urine recovery values could be demonstrated for the parenterally-administered antibiotics.