Vergleichende klinische Pharmakologie von Bacampicillin und hohen oralen Dosen von Ampicillin

Pharmacokinetics of phenoxymethylpenicillin was studied in 12 healthy volunteers. They received four different single oral dose sizes. At all dose levels (0.4, 1, 2 and 3 g) phenoxymethylpenicillin was rapidly absorbed, usually with serum peaks within 0.75 h. The mean maximal serum peaks ( ± SD) were 6.1 ± 2.0, 15.0 ± 4.3, 26.3 ± 10.0 and 35.5 ± 10.8 mg/l after 0.4, 1, 2 and 3 g, respectively. The relationship between the mean peak serum concentrations and the doses was nonlinear (p < 0.001). The mean areas under the serum concentrations vs. time curve (AUC) increased almost linearly with increasing doses, and the deviation from linearity was not significant (p < 0.05). Very low penicillin concentrations were obtained in saliva. The urinary excretion during 10 h was 37–43% of the doses given. The pharmacokinetic results indicated that phenoxymethyl penicillin in the present formulation is rapidly and well absorbed up to as high doses as 3 g. The tablet formulations used were better absorbed than previous ones. The percent of absorption was relatively lower with the highest doses, but this probably has only minor therapeutic consequences.

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“…The variation for individual AUC values was 20-30% which is comparable to values reported for ampicillin [12].…”

Section: Discussionsupporting

confidence: 66%

Pharmacokinetics of Phenoxymethylpenicillin in Volunteers

Josefsson

Bergan

1982

Chemotherapy

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“…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.…”

supporting

confidence: 92%

Bioavailability of Bacampicillin and Talampicillin, Two Oral Prodrugs of Ampicillin

Sjövall

Magni

Vinnars

1981

Antimicrob Agents Chemother

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A 200-mg amount of bacampicillin showed a significantly higher relative extent of bioavailability than did a 250-mg amount of talampicillin, possibly due to their different stability in the digestive juices.The prodrug technique is increasingly recognized as an approach to obtaining maximnum systemic concentrations in the body by the oral route (2). 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.The study was conducted in 10 male volunteers, 22 to 41 (mean 31) years old, with body weights ranging from 64 to 91 (mean 76) kg. All were healthy, as evidenced by routine clinical and laboratory examinations, and without known allergy to penicillins or cephalosporins. Before and after study, tests relevant to the renal and liver function, as well as hematological findings, were within normal ranges. Each subject received either a 200-mg (batch F162) or a 400-mg (batch F199) dose of bacampicillin hydrochloride (Penglobe; Astra Lakemedel AB, Sweden) or a 250-mg dose (batch 3902/A) of talampicillin hydrochloride (Talpen; Beecham Research Laboratories, England) in randomized order according to a complete crossover design with 1 week between experiments. After an overnight fast, the drugs were administered under supervision as single doses with 100 ml of water. Food was withheld for 3 h after medication. Intake of water was permitted ad libitum, except during the last hour before and the first hour after medication. The volunteers were instructed not to take any other drugs during the study. The study was approved by a peer review committee, and written informed consent was obtained.Blood samples were drawn from an antecubital vein before drug intake and 20 and 40 min, 1, 1.5, 2, 4, 6, and 8 h postmedication. Urine was collected at 2-h intervals during 8 h. All samples were stored at -20°C until analyzed. The ampicillin concentrations were determined by the cylinder-plate method, with Micrococcus luteus as test species (7). The detection limit in serum was 0.03 mg/liter. The relative extent of bioavailability was estimated by comparing the areas under the serum concentration versus time curves (AUC), calculated by the trapezoidal rule. A 200-mg amount of bacampicillin was used as standard in each subject. Areas were corrected for dose differences, calculated as anhydrous ampicillin. To test for significant differences in pharmacokinetic variables between drugs and doses (at the 5% level), the nonparametric Friedman analysis of variance was applied, followed by multiple comparisons based on the Friedman rank sums (3).None of the preadministration samples showed antibacterial activity. Both drugs were rapidly absorbed. The median time from tablet administration to the occurrence of the peak serum level was the same for all three doses, 40 min. The curves after 200 mg of b...

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“…for ampicillin pro-drugs where the proper choice of the ester form could provide an optimal balance between the decrease in dissolution rate and the increase in ab sorption rate [3]. Bacampicillin is such a pro-drug which is rapidly and extensively absorbed by the oral route [2,7,12], and which is well tolerated [9]. Bacampicillin itself has no antibiotic activity until it has been hydrolyzed to ampicillin, which sug gests less interference with the normal microflora, and thus less irritation after bacampicillin as compared to other types of antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Rectal Bioavailability of Bacampicillin Hydrochloride in Man as Determined by Reversed-Phase Liquid Chromatography

Sjövall¹,

Westerlund²,

Alván³

et al. 1984

Chemotherapy

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The relative bioavailability of bacampicillin hydrochloride, a pro-drug of ampicillin, was compared after rectal and oral administration. Bacampicillin was administered rectally as a microenema. The oral formulation was an aqueous microcapsule suspension. They were given as single doses of 400 mg to 12 healthy volunteers after overnight fasting using a randomized cross-over design. Ampicillin and bacampicillin were determined in plasma and blood, respectively, using HPLC. Bacampicillin was rapidly absorbed from the rectum but to a much smaller degree compared to the oral dose. The median t-max was 0.5 and 0.75 h after the rectal and oral doses, respectively. The mean (SD) C_p-max was 1.2 (0.33) mg/l after rectal and 4.8 (0.98) mg/l after oral administration, respectively. Blood concentrations of bacampicillin were extremely low or undetectable with no indication of differences between the two modes of administration. The 95% confidence limits for the relative bioavailability of the microenema were 22.4–39.2 and 22.5–40.4% based on area under the plasma concentration time curve and urinary recovery, respectively. The rectal dose was followed by distress, diarrhea or pain, in 7 subjects. There were no adverse reactions after the oral dose. Bacampicillin was unaffected by β-lactamases produced by intestinal bacteria.

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Vergleichende klinische Pharmakologie von Bacampicillin und hohen oralen Dosen von Ampicillin

Cited by 22 publications

References 13 publications

Pharmacokinetics of Phenoxymethylpenicillin in Volunteers

Pharmacokinetics of Phenoxymethylpenicillin in Volunteers

Bioavailability of Bacampicillin and Talampicillin, Two Oral Prodrugs of Ampicillin

Rectal Bioavailability of Bacampicillin Hydrochloride in Man as Determined by Reversed-Phase Liquid Chromatography

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