Pharmacology and Chemotherapy of Ampicillin—a New Broad‐spectrum Penicillin

Abstract

The pharmacology and chemotherapy of a new penicillin, 6[D(-)-a-aminophenylacetamido] penicillanic acid, are described. It is non-toxic, is absorbed orally and is distributed throughout the body in a manner similar to other penicillins. It is eliminated unchanged from the body in high concentrations in the bile and urine. Almost all of the antibiotic can be accounted for in the urine and intestinal contents 2 hr after intramuscular administration but not after oral administration. It is concluded that the antibiotic is not metabolized within the body. Studies with infected animals show that it is as effective as the existing oral penicillins against Staphylococcus pyogenes Smith (penicillin sensitive), Streptococcus pyogenes Group A and Diplococcus pneumoniae. It is ineffective against penicillin-resistant Staphylococci. When tested in mice infected with the gram-negative organisms, Salmonella typhimurium and Klebsiella pneumoniae, it was considerably more active than tetracycline and chloramphenicol.There is a need for a penicillin which is effective orally and having activity against both gram-negative and gram-positive organisms. Benzylpenicillin, although lacking in toxicity, is unfortunately not absorbed after oral administration and its activity against gram-negative organisms is limited. Doyle, Nayler & Smith (1961) have synthesized a new penicillin, ampicillin (6[D( -)-a-aminophenylacetamido] penicillanic acid), which largely overcomes these disadvantages. The preliminary pharmacology and chemotherapy has been reported by . Full details of the pharmacological and chemotherapeutic evaluation are now presented. METHODSIn all experiments benzylpenicillin was administered as its sodium salt. Ampicillin, which was 84% pure, was also administered as its sodium salt, all doses being given in terms of the pure compound. The antibiotics were assayed by the cup-plate technique using Sarcina lutea as the test organism. The zone diameters obtained for the control dilutions of the antibiotics were plotted against the log of the concentration, and from the regression line obtained the concentrations of the antibiotics in the specimens were estimated by interpolation. The appropriate dilutions of the controls and samples were made in phosphate buffer pH 7.0 <M/20) except in the experiments where serum concentrations were determined, in which case the controls were prepared in serum.Chromatographic studies were carried out using 1 cm wide strips of Whatman no. 1 filter papers, 53 cm long with the origin at 11 cm. The solvent used was ethyl acetate-isopropanolwater in the proportions 4:2: 1. 100 ml. of solvent was used in the trough of each tank.

Mechanism of Urinary Excretion of Cephaloridine and Its Effects on Renal Function in Animals

“…The extent of this tubular transport is small, especially when compared with the marked secretion of benzylpenicillin and methicillin (Acred, Brown, Turner & Wright, 1961) and ampicillin (Acred, Brown, Turner & Wilson, 1962). The results with cephaloridine are closely similar to those obtained with cloxacillin by Acred & Brown (1963), who observed that the percentage excretion after a 100-mg dose was only 5.8% greater on the injected side during the first hour after administration and that thereafter there was no difference in the percentage excreted by the two kidneys.…”

Pharmacokinetics and distribution of ticarcillin-clavulanic acid (Timentin) in experimental animals

“…The rat tissue distribution experiments showed that the pattern of distribution of ticarcillin and clavulanic acid was similar to that after administration of the two compounds in the ratio of 15:1 (10) and was not unlike that seen for other ,B-lactam compounds in rats (1). The concentrations in tissues generally depended upon vascularity and whether excretory processes were present.…”

1-Substituted carbamoyl and thiocarbamoyl-4,5-dihydro-1H-pyrazoles as possible cytotoxic and antimicrobial agents

“…The antifungal activity was tested using the pathogenic yeast strain Candida albicans (ATCC 10231) and Aspergillus niger (ATCC 16404). DMSO was used as a solvent control and the standard drugs used were Ampicillin 23 and Griseofulvin…”