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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 307 records · Page 17Linked to original sources
PubMed1988

The pharmacokinetics and tissue penetration of FCE 22101 following intravenous and oral administration.

One gram each of FCE 22101 and its acetoxymethyl ester (FCE 22891) were administered sequentially to six healthy volunteers. After intravenous administration Cmax was 167 mg/l, and the elimination half-life 0.8 h. Following oral administration Cmax was 6.9 mg/l and the elimination half-life 0.6 h. Penetration into inflammatory fluid was rapid, and the percentage penetration 86.1 and 60.9% following oral and intravenous dosing respectively. Urine recovery was greater after intravenous administration (31%) than after oral (11%).

Administration, Oral↗
PubMed1988

The penetration of fleroxacin into bronchial mucosa.

Twenty patients undergoing fibreoptic endoscopy received 400 mg of fleroxacin once a day for four days. Bronchial biopsies were performed 2.7-5.9 h following the final dose of fleroxacin. A microbiological assay was used to determine the levels of fleroxacin in serum and biopsy material. The serum levels of fleroxacin ranged from 3.9-12.5 mg/l (mean 8.4, S.D. 2.4). In all but one patient the bronchial mucosa level exceeded that in serum, the range being 5.9-19 mg/l (mean 12.8, S.D. 3.3). The mean percentage penetration into bronchial mucosa over the period of the study was 158% (S.D. 41.2%). The therapeutic implications are discussed.

Biopsy↗
PubMed1988

Pharmacokinetics and tissue penetration of cefpirome, a new cephalosporin.

The pharmacokinetics and tissue penetration (as measured by a blister fluid model) of cefpirome were studied in six male volunteers following a 1 g intravenous dose. A mean peak serum concentration (at 5 min) of 97.4 mg/l was followed by rapid distribution into an apparent volume of 21.3 1. The serum elimination half-life was 2.3 h. Cefpirome penetrated rapidly into inflammatory fluid with a mean peak concentration of 39.2 mg/l at 1.9 h. The mean inflammatory fluid elimination half-life was 2.5 h. The availability of the drug in inflammatory fluid was high with a mean per cent penetration of 123%. The plasma and renal clearances were 109.5 and 82.1 ml/min respectively. Twenty-four hour urinary recovery was 75.5% of the administered dose. This study suggests that a twice daily dosage may be sufficient to treat tissue infections with susceptible pathogens.

Adult↗
PubMed1988

A comparison of the pharmacokinetics and tissue penetration of spiramycin and erythromycin.

The pharmacokinetics of two orally administered macrolides, spiramycin and erythromycin, were compared in six healthy male volunteers in a single dose cross-over study. Penetration of these antimicrobial agents into inflammatory fluid was studied. Spiramycin was administered in a 2 g dose and erythromycin in a 500 mg dose. Spiramycin (Tmax = 3.3 h) and erythromycin (Tmax = 1.2 h) were well absorbed reaching mean plasma Cmax of 3.1 mg/l and 2.1 mg/l, respectively. The relative bioavailability of erythromycin compared to spiramycin appeared to be three- to four-fold greater. The mean plasma elimination half-life was 3.8 h for spiramycin and 1.6 h for erythromycin. The percentage penetration of the antibiotics into inflammatory fluid was good, being 66% for spiramycin and 54% for erythromycin. Both antimicrobial agents attained inflammatory fluid Cmax of 0.7 mg/l by 4-4.8 h. Spiramycin persisted in the inflammatory fluid with a mean elimination half-life of 7.7 h compared to 2.2 h for erythromycin. Twenty-four hour urinary recovery of the administered dose of each antimicrobial agent was less than 5%.

Adult↗
PubMed1988

The selection and frequency of streptococci with decreased susceptibility to ofloxacin compared with other quinolones.

Three strains each of Streptococcus pneumoniae, Lancefield group A streptococci, Lancefield group B streptococci and Lancefield group D streptococci were examined for the frequency of spontaneous mutation to give decreased susceptibility at two, four and six times the minimum inhibitory concentration of ofloxacin, ciprofloxacin, enoxacin and norfloxacin. Any putative mutants were examined for stability of resistance and susceptibility to all quinolones in the study, erythromycin and benzyl penicillin. All strains yielded mutants to twice the MIC of each quinolone at a frequency associated with a mutation at a single gene. Each species in the study responded differently at four and six times the MIC of each quinolone. Group B streptococci yielded most mutants and resistant Str. pneumoniae were the most difficult to select. Most mutants were cross-resistant to quinolones only, probably owing to an altered DNA gyrase. Fewer resistant mutants of Str. pneumoniae were selected using ofloxacin compared to ciprofloxacin.

Anti-Infective Agents↗
PubMed1988

The pharmacokinetics of ofloxacin and a review of its tissue penetration.

The pharmacokinetics of ofloxacin were studied in six healthy volunteers following a 600 mg oral dose. The concentration of the compound was measured in serum, inflammatory fluid and urine. Ofloxacin was rapidly absorbed, the mean maximum concentration of ofloxacin being 10.7 mg/l at 1.2 h. The mean serum elimination half-life was 7 h and 80.3% of the administered compound was recovered in the urine by 48 h. Ofloxacin penetrated the inflammatory fluid well, the mean peak level being 5.2 mg/l at 5.3 h. A review of the tissue penetration is presented which indicates that the high volume of distribution of ofloxacin is associated with good tissue penetration.

Adult↗
PubMed1988

The metabolism and pharmacokinetics of fleroxacin in healthy subjects.

A 400 mg dose of fleroxacin was administered orally to six healthy male volunteers. Concentrations of fleroxacin and the N-demethyl and N-oxide metabolites were determined in serum and urine by HPLC. The serum metabolite levels were negligible. The N-oxide metabolite was measured in the serum of five subjects but did not exceed 4% of the corresponding fleroxacin level. N-demethyl fleroxacin was not detected (less than 0.1 mg/l). The urinary recovery of fleroxacin was 49.5% over 72 h; the N-demethyl and N-oxide metabolites accounted for 6.9% and 5.7%, respectively, of the administered dose.

Anti-Infective Agents↗
PubMed1988

Pharmacokinetics and tissue penetration of orally administered lomefloxacin.

The pharmacokinetics of the quinolone lomefloxacin were determined following a single 400-mg oral dose given to each of six male volunteers. Concentrations in serum, urine, and cantharidin-induced inflammatory fluid were determined by a microbiological assay. Samples from two volunteers were also assayed by high-performance liquid chromatography. The mean peak level in serum, 4.7 micrograms/ml, was attained within 1 h of administration. The mean elimination half-life from serum was 7 h. Inflammatory fluid was penetrated rapidly, with a mean peak level of 3.5 micrograms/ml occurring after 2.7 h. The mean recovery of lomefloxacin from urine over 48 h was 76% of the administered dose. There was a minor peak on the high-performance liquid chromatography trace, suggesting a small amount of unidentified metabolite. This was present only in urine; no detectable metabolites were found in serum. This study suggests that either once-daily or twice-daily dosage of lomefloxacin should be sufficient to treat urinary or systemic infections, respectively, caused by susceptible pathogens.

4-Quinolones↗
PubMed1988

In vitro activity of lomefloxacin, a new quinolone antimicrobial agent, in comparison with those of other agents.

The in vitro activity of lomefloxacin (SC-47111; NY-198), a new difluorinated quinolone, was compared with those of ofloxacin, ciprofloxacin, fleroxacin, amoxicillin, cefuroxime, and trimethoprim against 585 recent clinical isolates and other strains with known mechanisms of resistance. The MICs of lomefloxacin against 90% of the members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and staphylococci were between 0.25 and 4 micrograms/ml. Ninety percent of Neisseria sp. and Haemophilus influenzae were susceptible to less than or equal to 0.06 micrograms/ml, and streptococci (including Streptococcus pyogenes, Streptococcus pneumoniae, and enterococci) and Bacteroides fragilis were susceptible to 8 micrograms/ml. Lomefloxacin was comparable in activity to fleroxacin and ofloxacin, but it was less active than ciprofloxacin. There was cross-resistance between the quinolone group of antimicrobial agents. The protein binding of lomefloxacin was 15.4%, and serum had little effect on the activity of the compound. However, urine at pH 5.0 decreased the activity by two- to eightfold compared with that at pH 7.0

Amoxicillin↗
PubMed1988

In vitro activity of PD 127,391, an enhanced-spectrum quinolone.

The in vitro activity of PD 127,391, a dihalogenated quinolone, was compared with those of ofloxacin, ciprofloxacin, nalidixic acid, gentamicin, and cefuroxime against 525 recent isolates and well-characterized antimicrobial agent-resistant strains. The MICs of PD 127,391 against 90% of members of the family Enterobacteriaceae, Bacteroides fragilis, Haemophilus influenzae, Neisseria sp., and Streptococcus pneumoniae were less than or equal to 0.12 microgram/ml. Some 90% of Pseudomonas aeruginosa and staphylococci were susceptible to 0.25 micrograms of PD 127,391 per ml. Against most strains, PD 127,391 was 2- to 8-fold more active than ciprofloxacin, but it was 64-fold more active than ciprofloxacin against B. fragilis. Strains of members of the family Enterobacteriaceae which were resistant to nalidixic acid were less susceptible to all of the quinolones tested, including PD 127,391. The MIC and minimum lethal concentration of PD 127,391 against three strains of Chlamydia trachomatis were each 0.06 microgram/ml, and the MIC against 90% of 21 strains of Mycobacterium tuberculosis was 1 microgram/ml. PD 127,391 was less active at pH 5, its maximal activity being at pH 7 to 8. The presence of urine at pH 5.9 decreased the bactericidal activity. The protein binding of PD 127,391 was 2 to 7%, and serum had little effect on activity.

Anti-Infective Agents↗
PubMed1988

Evaluation of the penetration of ciprofloxacin and amoxycillin into the bronchial mucosa.

The concentrations of two antibiotics, amoxycillin and ciprofloxacin, were measured by microbiological assay in serum and in bronchial mucosa obtained at fibreoptic bronchoscopy in 38 patients undergoing diagnostic bronchoscopy for a range of respiratory symptoms. Patients had taken one of the two drugs orally for four days before bronchoscopy. The percentage penetration of antibiotic from serum to bronchial mucosa was calculated as the ratio of drug concentration in bronchial tissue to that in serum x 100. Of the nine patients who took amoxycillin 500 mg thrice daily the mean (SD) percentage penetration was 75. This was significantly lower than the mean percentage penetration of 147 in 29 patients who took ciprofloxacin 500 mg twice daily. Ten patients were given a single intravenous dose of ciprofloxacin 200 mg one hour before bronchoscopy and the mean percentage penetration was 231. This study has shown that the quinolone antibiotic ciprofloxacin is concentrated in the bronchial mucosa.

Aged↗
PubMed1987

Tissue penetration and metabolism of ciprofloxacin.

The tissue penetration of ciprofloxacin was studied by two methods. Penetration into inflammatory fluid following oral administration (500 mg) was 117 percent; following intravenous administration (100 mg), penetration was 121 percent. The penetration of ciprofloxacin into uninflamed peritoneum following intravenous administration (100 mg) was 95 percent.

Administration, Oral↗