Bacampicillin: a New Orally Well-Absorbed Derivative of Ampicillin

Bodin, N.-O.; Ekström, Bertil; Forsgren, U; Jalar, L.-P.; Magni, L.; Ramsay, C.-H.; Sjöberg, Berndt

doi:10.1128/aac.8.5.518

Cited by 98 publications

(31 citation statements)

References 10 publications

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“…This is rapidly absorbed and transformed to ampicillin with a concomitant rapid breakdown of the ethoxycarbonyloxyethyl ester group to acetaldehyde, ethanol, and carbon dioxide. The hydrolysis proceeds so rapidly that no systemic bacampicillin has been detected (4). In animals, the new antibiotic is better absorbed than amp-iilin, giving higher and earlier peak blood,7evels of ampicillin (4, 9a).…”

Section: Othersmentioning

confidence: 99%

“…AUC -c(t) k2 (4) An estimation of the relative bioavailability was made by comparing the average areas under the serum concentration-time curves after bacampicillin with those of ampicillin and pivampicillin. Since amoxycillin is active as such and no, converted to ampicillin, the area under the serum concentrationtime curve cannot be used in a bioavailability comparison to the ampicillin drugs.…”

Section: Subjectsmentioning

confidence: 99%

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Pharmacokinetics of Bacampicillin Compared with Those of Ampicillin, Pivampicillin, and Amoxycillin

Sjövall

Magni

Bergan

1978

Antimicrob Agents Chemother

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Bacampicillin, a new oral prodrug which in vivo is rapidly transformed to ampicillin, was compared with ampicillin, pivampicillin, and amoxycillin in a randomized cross-over study on 11 healthy volunteers. All drugs were given in oral doses equimolar to 400 mg of bacampicillin (800 ,umol). The mean of the individual peak concentrations in serum was 8.3 jig/ml for bacampicillin, 7.1 ,ug/ml for pivampicillin, 7.7 ,ug/ml for amoxycillin, and 3.7 ,ug/ml for ampicillin. Furthermore, bacampicillin had a higher absorption rate than all the other drugs, although there were statistically significant differences only versus ampicillin. The peak serum levels of the individual subjects were more dispersed with ampicillin and amoxycillin, suggesting a more uniform absorption of bacampicillin and pivampicillin. The relative bioavailability of bacampicillin and pivampicillin was comparable, whereas ampicillin was only 2/3 that of the others.Ampicillin combines a low toxicity and broad antibacterial spectrum, but one disadvantage is its incomplete absorption. Small modifications of the molecule such as the insertion of a hydroxy group on the benzene ring in amoxycillin have improved absorption without essentially altering the antibiotic spectrum (27), although less activity in vitro against some species (3,21,32) and clinical inferiority (20) against Shigella have been noted in comparison with ampicillin. An improvement has been achieved by esterification of the carboxyl group with radicals which leads to increased lipid solubility and improved absorption. Upon uptake, the radicals are rapidly detached by hydrolysis, and free ampicillin is made available in blood and tissues. Examples of this class of compounds are pivampicillin (28, 29) and talampicillin (5, 25).A systematic search for a new ampicillin ester combining good bioavailability with virtual lack of gastrointestinal distress and diarrhea has led to bacampicillin [1'-ethoxycarbonyloxyethyl-6-(n-a-aminophenylacetamido)-penicillinate]. This is rapidly absorbed and transformed to ampicillin with a concomitant rapid breakdown of the ethoxycarbonyloxyethyl ester group to acetaldehyde, ethanol, and carbon dioxide. The hydrolysis proceeds so rapidly that no systemic bacampicillin has been detected (4). In animals, the new antibiotic is better absorbed than amp-iilin, giving higher and earlier peak blood,7evels of ampicillin (4, 9a).Studies with bacampicillin in healthy volunteers gave peak serum levels approximately 2.5 times higher than those after an equimolar dose of ampicillin. Mean individual peak serum levels after administration of 200, 400, and 800 mg of bacampicillin were 5.3, 8.9, and 16.5 ,ug/ ml, respectively (18). Bacampicillin has rendered bioavailabilities of 87 to 95% (26; T. Bergan, submitted for publication).With the various modifications of ampicillin and ampicillin-like antibiotics presently at the research stage, careful pharmacokinetic evaluations in controlled cross-over studies are important to reveal the points of distinction between them. The purpos...

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Section: Othersmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Pharmacokinetics of Bacampicillin Compared with Those of Ampicillin, Pivampicillin, and Amoxycillin

Sjövall

Magni

Bergan

1978

Antimicrob Agents Chemother

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“…Bacampicillin, a new semisynthetic penicillin, is a hydrochloride of the 1-ethoxycarbonyloxyethyl ester of ampicilin (4) Bacampicillin versus ampiciflin. Six volunteers were given 1,600 mg of bacampicillin (equivalent to 1,112 mg of ampicillin), and six were given 2,000 mg of ampicillin.…”

mentioning

confidence: 99%

Bacampicillin, Ampicillin, Cephalothin, and Cephapirin Levels in Human Blood and Interstitial Fluid

Tan

Salstrom

1979

Antimicrob Agents Chemother

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The diffusibility of bacampicillin, ampicillin, cephalothin, and cephapirin into human interstitial fluid was investigated by using crossover studies. We compared bacampicillin with ampicillin and found that bacampicillin was better absorbed after oral administration. Blood, interstitial fluid, and urine levels were consistently higher in volunteers who received bacampicillin. We compared cephalothin with cephapirin and found that blood and interstitial fluid levels were comparable throughout the study. Bacampicillin versus ampiciflin. Six volunteers were given 1,600 mg of bacampicillin (equivalent to 1,112 mg of ampicillin), and six were given 2,000 mg of ampicillin. Both drugs were given by mouth after an 8-h fast. The study was repeated after 1 week, and the volunteers received the drug that they had not received previously.Cephalothin (Keflin neutral) versus cephapirin (Cefadyl). Six volunteers were given 1 g of one drug over a 30-min period by intravenous infusion, and six were given 1 g of the other drug. The study was repeated after 3 weeks. The volunteers received the drugs which they had not received previously.Blood samples. Venous blood was obtained before and 0.5, 1, 1.5, 2, 3, 4, and 5 h after administration of bacampicillin or ampicillin. The serum was separated after 45 min at 240C and immediately frozen. Venous blood was obtained before and 0.5, 1, 2, 3, and 4 h after the start of intravenous infusion of cephalothin or cephapirin. Blood was drawn into a heparinized tube to reduce deacetylation of the cephalosporins, and the plasma was separated and immediately frozen.Interstitial fluid samples. The technique of obtaining interstitial fluid by using a skin window chamber has been described previously (13).Urine sampling. Urine samples from six volunteers receiving bacampicillin and six receiving ampicillin were collected at 2, 4, and 5 h after antibiotic administration.Assay of antibiotics. Antibiotics were assayed by the agar well technique described by Bennett et al.(2), using a Bacillus subtilis spore suspension (Difco Laboratories, Detroit, Mich.) as the test organism. Pooled human plasma was used as the diluent for the standards of the serum and plasma antibiotic assay. Phosphate-buffered saline (pH 6) was used to dilute the standards for the skin window fluid assay. RESULTSBacampicillin versus ampicillin. The dose of bacampicillin administered was approximately half that of ampicillin, yet the serum antibiotic concentrations after the administration of bacampicillin consistently were higher during the first 3 h (Table 1). Similarly, the interstitial fluid levels of bacampicillin were also consistently higher. The serum and skin window fluid ratios were almost identical throughout the 5 h of the study.At the end of 5 h, volunteers who received ampicillin excreted in the urine an average of 492 mg of ampicillin, which is equivalent to 25% of the ingested dose. Volunteers who received bacampicillin excreted an average of 701 mg of ampicillin, which is equivalent to 63% of the ingested dose.Ceph...

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“…The in vitro synergism against the same organisms is included for comparison with in vivo synergism. The oral prodrug of ampicillin, bacampicillin, was used in the in vivo experiments since it is better absorbed than ampicillin and since, after absorption, it is rapidly hydrolyzed to give high serum levels of ampicillin (1). The greatest potentiation of ampicillin activity occurred against two Proteus mirabilis isolates.…”

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confidence: 99%

6 beta-Iodopenicillanic acid (UI-38,006), a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactam compounds: initial bacteriological characterization

Moore¹,

Brammer²

1981

Antimicrob Agents Chemother

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Bacampicillin: a New Orally Well-Absorbed Derivative of Ampicillin

Cited by 98 publications

References 10 publications

Pharmacokinetics of Bacampicillin Compared with Those of Ampicillin, Pivampicillin, and Amoxycillin

Pharmacokinetics of Bacampicillin Compared with Those of Ampicillin, Pivampicillin, and Amoxycillin

Bacampicillin, Ampicillin, Cephalothin, and Cephapirin Levels in Human Blood and Interstitial Fluid

6 beta-Iodopenicillanic acid (UI-38,006), a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactam compounds: initial bacteriological characterization

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