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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 289 records · Page 16Linked to original sources
PubMed1989

Pharmacokinetics and tolerance of a new film-coated tablet of sodium fusidate administered as a single oral dose to healthy volunteers.

Single oral doses of 250, 500, 750 and 1000 mg of sodium fusidate as one, two, three and four film-coated 250 mg tablets were compared in a cross over design trial with a solution dose of 500 mg in 12 healthy male volunteers. The effect of food on absorption of two-film coated tablets was also studied. Compared with the dose given as a solution, tablets gave complete oral absorption, the area under the curve (AUC) for blood concentration being virtually identical. After administration of 250, 500, 750 and 1000 mg the mean of the maximum serum concentrations (Cmax) was 11.6 +/- 1.1, 30.6 +/- 2.2, 48.1 +/- 3.0 and 65.2 +/- 4.2 mg/l, respectively, indicating a greater than expected increase in Cmax with increasing dose. This was also apparent with AUC, while there was a significant trend for beta, the terminal slope of the serum/concentration time curve, to decrease. Food significantly reduced Cmax and delayed Tmax but did not affect AUC or beta. Dosage had no effect on parameters of renal, hepatic or haemopoietic function but 25% of the volunteers complained of upper gastro-intestinal symptoms mainly at the highest dose studied.

Administration, Oral↗
PubMed1989

Activity of FCE 22101 against methicillin-resistant Staphylococcus aureus and affinity for penicillin binding proteins.

The susceptibility of 47 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to FCE 22101, imipenem and methicillin was determined with Iso-Sensitest media, with or without NaCl and with incubation at 30 degrees and 37 degrees C and for 24 and 48 h. All strains had a MIC 8 mg/l of methicillin under at least one of the culture conditions. The MIC90 of FCE 22101 was 1 mg/l, and that of imipenem 16 mg/l. The affinity of FCE 22101 for the penicillin-binding proteins (PBPs) of five clinical isolates of MRSA and S. aureus 13136 p-m+ was examined in envelope preparations and whole cell assay under the growth conditions listed above. PBP 2' was detected in all MRSA, and the clinical isolates had an I50 of 4 mg/l FCE 22101. These in-vitro data suggest that FCE 22101 may be active against MRSA in clinical use.

Anti-Bacterial Agents↗
PubMed1989

Review of the in-vitro evaluation of FCE 22101.

FCE 22101 is a broad spectrum beta-lactam displaying bactericidal properties, stable to a wide range of clinically relevant beta-lactamases, and sharing with other beta-lactams a modest post-antibiotic effect and synergistic interactions with aminoglycosides. The ability to administer the drug by oral and parenteral routes suggests that it could be clinically useful.

Anti-Bacterial Agents↗
PubMed1989

Pharmacokinetics and tissue penetration of cefepime.

The pharmacokinetics of cefepime were studied following a 2 g intravenous infusion, by measuring concentrations in plasma, inflammatory fluid and urine. Mean peak plasma concentrations of 193.1 mg/l were achieved at the end of the 30 min infusion. The mean plasma elimination half-life was 2.1 h. Penetration into inflammatory fluid was rapid, with mean peak levels of 91.5 mg/l occurring 0.9 h after the end of the infusion. Urinary elimination accounted for 98.9% of the dose within 8 h. Therapeutic plasma levels (greater than 2 mg/l) were present for at least 8 h after the end of the infusion, suggesting that twice or three times daily dosing should be sufficient to treat infections due to susceptible organisms.

Adult↗
PubMed1989

The in-vitro activity, pharmacokinetics and tissue penetration of temafloxacin.

The in-vitro activity of temafloxacin compared with other quinolone antibiotics was evaluated using 579 bacterial strains and three isolates of Chlamydia trachomatis. The MICs of temafloxacin for 90% of Haemophilus influenzae, Neisseria spp., Enterobacteriaceae, Bacteroides fragilis and Ch. trachomatis were all less than or equal to 1 mg/l, an activity comparable with or superior to that of ofloxacin and superior to those of fleroxacin and norfloxacin. Temafloxacin, although more active against anaerobes, was in general slightly less active than ciprofloxacin. Against Streptococcus pneumoniae and Staphylococcus aureus (including MRSA) temafloxacin was twice as active as ciprofloxacin. The pharmacokinetics of temafloxacin were studied in six volunteers, following a single 400 mg oral dose, measuring concentrations in plasma, inflammatory fluid and urine. Mean peak plasma levels of 3.3 mg/l were achieved. The mean plasma elimination half life was 6.8 h and the percentage penetration into blister fluid was 104.5%. Of the administered dose 51.8% was excreted in urine by 26 h. Serum and blister fluid levels in excess of 1 mg/l were present for at least 8 h post dose, suggesting that a once or twice daily dosing regimen would be suitable for the treatment of infections caused by susceptible organisms.

4-Quinolones↗
PubMed1989

A simple isocratic high-pressure liquid chromatographic assay of quinolones in serum.

A simple HPLC assay was evaluated for the analysis of ciprofloxacin, enoxacin, fleroxacin, lomefloxacin, norfloxacin, ofloxacin and pefloxacin and their available metabolites in serum. A reverse-phase column was used with an acidic mobile phase containing heptane sulphonic acid. Two reverse-phase columns of similar selectivity but different efficiencies were used. The eluate was monitored by UV or fluorescence detection. Serum was prepared for assay by protein precipitation with acids which yielded high recoveries with good reproducibility (CV less than 2.5%). Absorbance maxima and optimum fluorescence detection parameters were determined for each quinolone. Assay specificity, tested by analysing serum from 20 hospital patients, was good. Analysis of patient and volunteer sera for enoxacin and fleroxacin showed good agreement with a microbiological method (regression coefficients greater than 0.956). A single, specific analytical method applicable to the quinolone group may be simpler and cheaper for the clinical laboratory. The assay described here provides a simple to perform, sensitive and specific method for quantitation of several quinolones and their metabolites.

4-Quinolones↗
PubMed1989

The effect of mutations in the SOS response on the kinetics of quinolone killing.

The SOS response is induced in Escherichia coli by agents that damage DNA, such as quinolone antibiotics. It has been proposed that induction of the SOS response by these agents may have a role in the mechanism of quinolone action. SOS mutants derived from Escherichia coli AB1157 were investigated by susceptibility testing and killing kinetic studies at various quinolone concentrations to determine whether SOS response induction was protective or damaging to quinolone-treated bacteria. Susceptibility testing showed some differences between the SOS mutants, but killing kinetic studies demonstrated further differences, some of which could be explained with respect to the SOS phenotype. The effect of ciprofloxacin and nalidixic acid on the mutants cannot be explained with respect to the SOS phenotype, although the presence of a defective SOS response makes the bacteria less sensitive to the action of these agents. Evidence is provided that the induction of the SOS response may be protective to fleroxacin and enoxacin treated bacteria. These results suggest that quinolones may not have a common mechanism of action, as was first thought.

4-Quinolones↗
PubMed1989

The antibacterial activity of meropenem in combination with gentamicin or vancomycin.

The kinetics of bacterial killing by meropenem alone and in combination with gentamicin (for Pseudomonas aeruginosa) and vancomycin (for Staphylococcus aureus) were studied for two strains of each species. Against the two strains of P. aeruginosa, meropenem at concentrations up to 4 x MIC was rapidly bactericidal--but regrowth occurred by 24 h. The addition of half the MIC of gentamicin to the MIC of meropenem led to a more rapid decline of the colony count and to the prevention of regrowth of the strain which was gentamicin-susceptible. Similar results were obtained for a methicillin-susceptible strain of S. aureus when vancomycin was added at a concentration of half the MIC. A methicillin-resistant strain also was killed by a combination of vancomycin at half the MIC plus meropenem at the MIC. The study showed that the killing action of meropenem against P. aeruginosa and staphylococci is enhanced by the addition of gentamicin or vancomycin respectively.

Carbapenems↗
PubMed1989

The in vitro activity of tigemonam: a comparison with other antimicrobial agents.

The activity of tigemonam was compared with that of aztreonam, cefuroxime, cephalexin, amoxicillin/clavulanate potassium, gentamicin, and ofloxacin, using an agar dilution method. Tigemonam was active against strains containing known beta-lactamases of Tem and Oxa types, but strains containing broad-spectrum (group IV) enzymes were less susceptible. The MIC90 of tigemonam against the common Enterobacteriaceae was less than or equal to 0.25 mg/L. The MIC90S against Haemophilus influenzae and Neisseria gonorrhoeae were 0.5 and 0.06 mg/L, respectively. Pseudomonas, staphylococci, and Bacteroides sp. were less susceptible (MIC90 greater than 128 mg/L). Protein binding in human serum was found to be 62.5%; the presence of serum had only a modest effect on the activity of tigemonam.

Enterobacteriaceae↗
PubMed1988

The pharmacokinetics and tissue penetration of intravenously administered CGP 31608.

The pharmacokinetics of CGP 31608, a new injectable penem antibiotic, were studied following a 1 g intravenous infusion. Concentrations were determined in serum, urine and cantharidin-induced inflammatory fluid by a microbiological assay. Peak serum concentrations were achieved at, or before the end of, the 1 h infusion, with a mean of 24.9 mg/l occurring at 0.8 h. The mean serum elimination half-life was 0.5 h, with no detectable drug in serum after 3 h. Inflammatory fluid was penetrated rapidly with a mean peak level of 10.5 mg/l occurring at 1.3 h (i.e. 20 min after the end of the infusion). Urinary elimination of CGP 31608 accounted for 52.1% of the administered dose within an hour of finishing the infusion, and 57.1% by 12 h. This study suggests that therapeutic serum levels (greater than 8 mg/l) are present for about 1.5 h after starting a 1 h infusion, and in inflammatory fluid for about 2.5 h. Unless a dose in excess of 1 g is used, CGP 31608 will probably have to be given four or more times a day.

Adult↗