4800-94-6

Carbenicillin is a broad-spectrum carboxypenicillin antibiotic. It is active against Gram-negative and certain Gram-positive bacteria, including S. pyogenes, S. epidermidis, P. mirabilis, P. vulgaris, E. coli, and P. aeruginosa (MICs = 0.19, 1.56, 1.56, 3.12, 3.12, and 50 μg/ml, respectively). It is also active against penicillinase-producing and non-producing strains of S. aureus (MICs = 1.56 and 12.5 μg/ml, respectively). Carbenicillin is protective against systemic S. pyogenes, P. vulgaris, E. coli, and S. aureus infection in a mouse model of systemic lethal infection with 50% protective dose (PD₅₀) values of 7.8, 224, 19.3, and 34 mg/kg, respectively. It also decreases viable colony counts in the kidney in a rat model of P. vulgaris or E. coli urinary tract infection when administered at a dose of 100 mg/kg. Formulations containing carbenicillin have previously been used in the treatment of upper and lower urinary tract infections and prostatitis.

white Powder

Pyopen,Beecham,Switz.,1968

Semi-synthetic antibiotic related to Penicillin (P223500). Antibacterial.

ChEBI: Carbenicillin disodium is an organic sodium salt. It contains a carbenicillin(2-).

The required monobenzyl phenylmalonate, MP 68°C, was prepared by treating a mixture of phenylmalonic acid (18 g) and benzyl alcohol (13 g) in carbon tetrachloride (80 ml) with dry hydrogen chloride.
Monobenzyl phenylmalonate (13.3 g) in dry benzene (100 ml) was refluxed with thionyl chloride (6.45 g) for 90 minutes, then concentrated in vacuo. The residual oil was dissolved in dry acetone (50 ml) and added to a stirred, ice-cooled solution of 6-aminopenicillanic acid (9.7 g) in N sodium bicarbonate solution (135 ml), water (150 ml), and acetone (300 ml). The mixture was stirred for 30 minutes at 0°C and then for 90 minutes at room temperature, then concentrated under reduced pressure to remove acetone. The aqueous solution was brought to pH 2 with dilute hydrochloric acid and extracted with ether (3 x 100 ml). The ether solution was washed with water and then itself extracted with sufficient N sodium bicarbonate solution to give an aqueous phase of pH 7.5. The aqueous layer was separated and evaporated at low temperature and pressure to leave the impure sodium salt of alpha- (benzyloxycarbonyl) benzylpenicillin.
This crude product (15.8 g) in water (360 ml) was added to a prehydrogenated suspension of 10% palladium on charcoal (4 g) in water (400 ml), and hydrogenation was continued for 30 minutes. The catalyst was removed and the filtrate was adjusted to pH 7.5 with sodium bicarbonate, then evaporated at low temperature and pressure. The residue was purified by chromatography on a column of cellulose powder, eluting first with butanol/ethanol/water mixture and then with acetone/isopropanol/water. The main fraction was evaporated at low temperature and pressure to give a 32% yield of the sodium salt of alpha-carboxybenzylpenicillin as a white powder. The product was estimated by monometric assay with penicillinase to be 58% pure.

Geopen (Roerig); Pyopen (GlaxoSmithKline).

Antibacterial

Analog to ampicillin . Inhibits bacterial cell-wall synthesis (peptidoglycan cross-linking) by inactivating transpeptidases on the inner surface of the bacterial cell membrane. Effective against Gram-positive and Gram-negative bacteria and Pseudomonas.

Carbenicillin disodium, disodium α-carboxybenzylpenicillin(Geopen, Pyopen), is a semisynthetic penicillin releasedin the United States in 1970, which was introduced inEngland and first reported by Ancred et al. in 1967.Examination of its structure shows that it differs from ampicillinin having an ionizable carboxyl group rather than anamino group substituted on the α-carbon atom of the benzylside chain. Carbenicillin has a broad range of antimicrobialactivity, broader than any other known penicillin, a propertyattributed to the unique carboxyl group. It has been proposedthat the carboxyl group improves penetration of themolecule through cell wall barriers of Gram-negativebacilli, compared with other penicillins.
Carbenicillin is not stable in acids and is inactivated bypenicillinase. It is a malonic acid derivative and, as such, decarboxylatesreadily to penicillin G, which is acid labile.Solutions of the disodium salt should be freshly prepared but,when refrigerated, may be kept for 2 weeks. It must be administeredby injection and is usually given intravenously.
Carbenicillin has been effective in the treatment of systemicand urinary tract infections caused by P. aeruginosa,indole-producing Proteus spp., and Providencia spp., all ofwhich are resistant to ampicillin. The low toxicity of carbenicillin,with the exception of allergic sensitivity, permits theuse of large dosages in serious infections. Most cliniciansprefer to use a combination of carbenicillin and gentamicinfor serious pseudomonal and mixed coliform infections. Thetwo antibiotics are chemically incompatible, however, andshould never be combined in an intravenous solution.