6-β-Bromo- and 6-β-iodo penicillanic acid, two novel β-lactamase inhibitors

Wise, R.; Andrews, J. M.; Patel, Nandesh

doi:10.1093/jac/7.5.531

Cited by 38 publications

(10 citation statements)

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“…It is of interest that the differences in the AUC ratios for the drug are less than those for the Cmn ratios, providing some evidence that the differences may be more readily explained by a smaller transfer rate constant. In general, brobactam inhibits the same range of ,B-lactamases as clavulanic acid and has a similar (or somewhat less) potency in i-lactamase inhibition (4,8). The levels of ampicillin and brobactam achieved in serum are generally similar to those found for amoxicillin and clavulanic acid following a dose of 250 mg/125 mg (5), a commonly employed regimen.…”

Section: Discussionmentioning

confidence: 75%

Pharmacokinetics and tissue penetration of ampicillin and brobactam following oral administration of 2085P

Wise

O’Sullivan

Johnson

et al. 1992

Antimicrob Agents Chemother

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Eight healthy volunteers received a 1,000-mg single oral dose of 2085P which consisted of 800 mg of pivampicillin and 200 mg of brobactam. Concentrations of ampicillin and brobactam in plasma, inflammatory fluid, and urine were measured over the subsequent 24 h. Pivampicillin and brobactam were moderately rapidly absorbed. The mean (standard deviation) maximum concentration in plasma (C..) of ampicillin was 8.2 (1.9) ,uglml, and that of brobactam was 2.1 (2.0) ,ug/ml at mean times of 1.9 (0.5) and 2.3 (0.8) h, respectively. The elimination half-lives in plasma were 1.8 (0.5) and 1.6 (2.0) h, respectively. Both agents penetrated the experimentally induced inflammatory fluid, reaching a mean maximum at 3 h. The Cmax of ampicillin was 6.8 (2.3) tag/ml, and that of brobactam was 1.0 (0.4) ,ug/mI. The penetration (derived by comparing the area under the concentration-time curve from 0 h to infinity for inflammatory fluid with that for plasma) was 97.3% (26.0%o) for ampicillin and 81% (22.3%) for brobactam. The 24-h urinary recovery was 54.2% (16.6%,) of the administered dose for ampicillin and 40.2% (11.4%) for brobactam. These data suggest that this combination of P-lactam and inhibitor should be efficacious in treating infections caused by ampicillin-resistant pathogens.Brobactam, or 6-f-bromopenicillanic acid, is a P-lactamase inhibitor similar to clavulanic acid (3). Pivampicillin is an oral prodrug of ampicillin (7) and is an organic base capable of reacting with an equimolar amount of an organic acid, such as brobactam, to form an addition salt, pivampicillin 6-0-bromopenicillanate. 2085P is a combined preparation of pivampicillin 6-p-bromopenicillanate and additional pivampicillin that contains pivampicillin and brobactam in a fixed 4:1 (wt/wt) ratio.In this study, we have investigated the pharmacokinetic properties of ampicillin and brobactam after oral administration of a single dose of 2085P and determined their penetration into a chemically induced inflammatory exudate (9). ,ug/ml, and the coefficient of variation between assays was 7.7% at 0.8 p,g/ml and 6.5% at 6 jig/ml; the within-assay coefficients of variation were 6 and 7.2%, respectively. Ampicillin was assayed with antibiotic medium no. 2 (Oxoid) and Micrococcus lutea as indicator organism. The lower limit of sensitivity was 0.03 ,ug/ml, and the coefficients of variation between assays were 9.5% at 0.4 ,ug/ml and 10.7% at 3 p,g/ml; the within-assay coefficients of variation were 11.6 and 11.8%, respectively. MATERIALS AND METHODS

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Section: Discussionmentioning

confidence: 75%

Pharmacokinetics and tissue penetration of ampicillin and brobactam following oral administration of 2085P

Wise

O’Sullivan

Johnson

et al. 1992

Antimicrob Agents Chemother

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“…6[J-Iodopenicillanic acid has also been reported to be an inhibitor of [J-Iactamases (KEMP et al 1980). Both 6[J-bromo-and 6[J-iodopenicillanic acids have been shown to exhibit synergistic activity with ampicillin comparable to that of clavulanic acid and greater than that of sulbactam (WISE et al 1981). Similarly, BL-P 2013 (Fig.…”

Section: -N-!"ch3mentioning

confidence: 93%

β-Lactam Antibiotics: Structure-Activity Relationships

Hoover¹

1983

Antibiotics

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“…Many other P-lactamase inhibitors have been described in the literature. Among these are the halopenicillanic acids, with a spectrum of activity similar to that of clavulanic acid (85,118,144), other penicillanic acid sulfones (59? 101, 146), and carbapenems (20,74,109,111).…”

Section: Mechanisms Of Action: Specificmentioning

confidence: 99%

Beta-lactamase inhibitors from laboratory to clinic.

Bush

1988

Clinical Microbiology Reviews

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6-β-Bromo- and 6-β-iodo penicillanic acid, two novel β-lactamase inhibitors

Cited by 38 publications

References 0 publications

Pharmacokinetics and tissue penetration of ampicillin and brobactam following oral administration of 2085P

Pharmacokinetics and tissue penetration of ampicillin and brobactam following oral administration of 2085P

β-Lactam Antibiotics: Structure-Activity Relationships

Beta-lactamase inhibitors from laboratory to clinic.

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