摘要:

In vivo models in rodents and primates were used to investigate ways of overcoming the poor oral and rectal absorption of ceftriaxone. The sodium salt of ceftriaxone at 20 mg/kg was formulated in C8-C10 chain length, mono- and diglyceride extracts of coconut oil (Capmul) and adminstered intraduodenally to adult rats. Peak plasma levels of 17–52 μg/ml and bioavailability averaging 38% were attained. Significant plasma levels (42–45 μg/ml) were also demonstrated in squirrel monkeys with doses of 20 mg/kg ceftriaxone formulated in Capmul and given by the enteral route. Enteric-coated capsules containing this formulation were also orally administered to squirrel monkeys and gave high plasma levels (10–31 μg/ml) between 1 and 6 h following dosing. In rectal absorption studies, ceftriaxone formulated in Capmul as a suspension gave peak blood levels of 62–84 μg/ml (average bioavailability 42%) in the rabbit. In the baboon, rectal administration of ceftriaxone formulated with Capmul in a Witepsol HI5® suppository gave Cmax levels ranging from 9 to 48 μg/ml, depending on the dose of the antibiotic and the drug/e

ISSN:0009-3157    

DOI:10.1159/000238551

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The pharmacokinetics of bacampicillin, a prodrug of ampicillin which is absorbed from the gastrointestinal tract, were studied in 10 healthy male volunteers after administration of 1,200 mg in a single oral dose. The pharmacokinetic analysis was carried out by applying a single-compartment kinetic model with zero-order absorption. The apparent duration of absorption (T) was about 1 h for all subjects. The peak plasma concentrations (Cmax) were 17.89 ± 1.82 μg/ml, and the mean plasma half-life during β-phase was 1.17 ± 0.14 h. The area under the curve was 41.22 ± 5.29 μg . h/ml. The mean urinary recovery during 24 h amounted to 76.4 ± 3.65 % of th

ISSN:0009-3157    

DOI:10.1159/000238552

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Lipophilicity of the injectable form of some antibiotics was measured with a micromethod. The antibiotic was dissolved in a small volume (1 ml) of phosphate buffer at a physiological pH (pH = 7.4) and was extracted by a small volume of octanol (1 ml). HPLC determinations of the antibiotic were performed in the two phases, log P ranged from +1.3 for chloramphenicol to -4.3 for ceftriaxone. A linear relationship was established for a few antibiotics between the log P values found in our experiments and the log permeability calculated from data in the literature for human and rat brain. This linear relationship enabled the brain concentrations of antibiotics to be predicted in man and rats.

ISSN:0009-3157    

DOI:10.1159/000238553

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Combination of ketoconazole and trifluoperazine or chlorpromazine yielded an in vitro synergistic effect on growth inhibition of Candida albicans, Torulopsis glabrata, Cryptococcus neoformans, Candida parapsilosis and Candida tropicalis. The optimal pH range for the synergistic effects was 7.0–7.6. At pH 5.0 the drug combination was antagonistic. (Application for patent protection has been filed

ISSN:0009-3157    

DOI:10.1159/000238554

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The fluoroquinolones ciprofloxacin, norfloxacin, and ofloxacin were examined in vitro against 103 enterococcal isolates and 138 isolates of Pseudomonas aeruginosa, in an attempt to determine which respective proposed interpretive criteria (minimal inhibitory concentration (MIC) versus diameter of agar disk diffusion inhibition zones) correlated best, i.e., resulted in fewer discrepant results. A previously proposed system for grouping discrepant results (very major, major, and minor discrepancies) of Barry and co-workers was modified to comprise 6 categories (very major, major, minor, slight, minimal, and negligible); this expanded system rendered the encountered discrepant in vitro test results more transparent. Overall, the currently employed interpretive criteria for norfloxacin (MICs versus 10-μg disks) resulted in fewer discrepancies with the above two groups of bacterial isolates than those proposed for ciprofloxacin and ofloxacin (MICs versus 5-μg disks, respectively

ISSN:0009-3157    

DOI:10.1159/000238555

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

We tested 42 strains of amikacin-resistant gram-negative bacilli with amikacin in combination with six beta-lactam antibiotics using the checkerboard and time-kill curve techniques. Synergism was demonstrated with time-killing curve in 43–68% of the strains tested. Ceftazidime plus amikacin was the most active combination by the checkerboard technique, while amikacin-cefoperazone was the most active combination by the time-killing curve technique against Pseudomonas aeruginosa. Discrepancies were found between the results of the two methods use

ISSN:0009-3157    

DOI:10.1159/000238556

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The susceptibilities of 121 streptococcal strains isolated from patients with infective endocarditis to mezlocillin, piperacillin, ceftizoxime, ceftriaxone, ceftazidime, imipenem, ciprofloxacin, ofloxacin and pefloxacin were determined by the agar dilution technique. Viridans streptococci, Streptococcus bovis and Enterococcus faecalis were susceptible to imipenem, mezlocillin and piperacillin. All the strains, except E. faecalis were sensitive to ceftriaxone, ceftizoxime and ceftazidime and resistant to ciprofloxacin, ofloxacin and pefloxacin. E. faecalis strains were moderately resistant to the new quinolons.

ISSN:0009-3157    

DOI:10.1159/000238557

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The antibacterial activity of imipenem combined with norfloxacin, ciprofloxacin, or ofloxacin against 43 gram-positive cocci and 53 aerobic gram-negative rods isolated from hospitalized patients was determined by the checkerboard method and compared to results obtained with the combination of imipenem with amikacin. Synergistic antibacterial action (defined as FIC index ≤ 0.5) was found for 28% of strains with imipenem/amikacin and imipenem/norfloxacin, in 23% with imipenem/ofloxacin, and in 18% with imipenem/ciprofloxacin. Antagonistic activity (FIC index > 1.0) was found in 21, 21, 32, and 23% respectively. These rates were not statistically different for gram-positive and gram-negative isolates. Antagonistic activity seemed to occur more frequently with Pseudomonas spp. and enterococci than with staphylococci or Entero-bacteriaceae. A tendency for increased rates of antagonism was noted in strains with higher MIC values. Clinically significant and meaningful positive interactions (defined as a decrease of imipenem MICs to below 2.0 (μg/ml) were found with imipenem/amikacin against several Pseudomonas spp., with imipenem/ofloxacin or ciprofloxacin against Streptococcus faecium and with all combinations against Proteus spp. We conclude that continuous treatment with newer quinolone derivatives for selective decontamination in neutropenic patients receiving imipenem antibacterial therapy for treatment of infection should not be regarded as effective combination thera

ISSN:0009-3157    

DOI:10.1159/000238558

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Some acridine compounds referred to as 9-imino, 9-oxo and 9-thio derivatives were screened for activity against Trypanosoma cruzi in vitro. The results are discussed here with reference to the structure of the compounds tested. Attempts to elucidate the mode of action of active acridines are also included. The most active compounds that were tested were 9-thioacridanones and 9-thio-1,2,3,4-tetrahydroacrida-nones. Added to this, the dialkylaminoalkylthio group seems to be the most convenient molecular moiety for trypanocidal activity in the 9-substituted acridine series.

ISSN:0009-3157    

DOI:10.1159/000238559

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Electron microscopic studies of sarcoma-180 ascites cells, which were treated with platinum-thymine at a concentration of 60 μg/ml, showed mitotic inhibition. The drug clumped the chromosomes into a compact mass at the center of the cell preventing them from separating during mitosis. Prolonged treatment depolymerized spindle fibers and cytoplasmic microfilament. Degraded cytoplasmic organelles crowded around the clumped chromosomes. Disintegrating and casting off of cortical cytoplasm was apparent. Platinum-thymine-treated cells did not resume mitosis irrespective of the amount of time they were allowed to remain in fresh medium. Perturbation of mitotic machinery by platinum-thymine inhibited the mitotic process and caused eventual demise of the cancer cells

ISSN:0009-3157    

DOI:10.1159/000238560

出版商:S. Karger AG    

年代:1988

数据来源: Karger