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

Abstract

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...

Bioavailability of Bacampicillin and Talampicillin, Two Oral Prodrugs of Ampicillin

“…The serum concentrations found in this study are, in general, compatible with previous reports (4)(5)(6)(7)(8). The coefficient of variation in individual peak serum concentrations of approximately 20% after all doses is in agreement with previous results with bacampicillin (7,8), pivampicillin (8), and talampicillin (9), verifying a uniform and reliable absorption of these prodrugs.…”

“…Several prodrugs of ampicilhin, such as bacampicillin, pivampicilhin, and talampicillin, have been made. The pharmacokinetics of bacampicillin and pivampicillin were compared in a previous report (8). The purpose of the present study was to compare the bioavailabilities of bacampicillin and talampicillin.…”

Biotransformation and Rearrangement of Laromustine

“…Pivampicillin, talampicillin, and bacampicillin are prodrugs of ampicillin, each of which is produced from the esterification of the polar carboxylate group to form lipophilic, enzymatically labile esters (Sjövall et al, 1978;Ehrnebo et al, 1979;Ensink et al, 1996). These prodrugs result in nearly total absorption, whereas that of ampicillin is ,50%.…”

Comparative study of bacampicillin and ampicillin in the treatment of uncomplicated gonorrhoea.

“…In studies by Wiesner et al3 and Bro-Jorgensen and Jensen4 of patients who had positive culture results for Neisseria gonorrhoeae at genital, rectal, or pharyngeal sites, pharyngeal colonisation rates ranged from 10-10 3 % in women, 3 * 2-6% in male heterosexuals, and 20 ' [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Follow-up visits took place 5-9 days after treatment, at which time patients were questioned about symptoms and possible drug-related reactions. Gram stains, cultures, wet-mount preparations, urine analyses, and tests to monitor for adverse drug reactions were repeated as for the initial visit.…”