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Biomedical subjects

D Honeybourne

Publications and source records attributed to D Honeybourne.

At least 19 recordsLinked to original sources
PubMed1992

Concentrations of cefpodoxime in serum and bronchial mucosal biopsies.

Cefpodoxime proxetil is a new orally administered cephalosporin which has a favorable spectrum of activity against respiratory pathogens. Concentrations of cefpodoxime in serum and bronchial mucosal biopsy were measured in 13 patients without active respiratory tract infection undergoing fibreoptic bronchoscopy. Samples were taken between 1 and 6 h after a single oral dose of cefpodoxime proxetil equivalent to 200 mg of cefpodoxime base. In twelve patients who completed the study, mean serum concentrations were 1.7 mg/L (S.E.M. 0.4) and in ten patients mean bronchial biopsy concentrations were 0.9 mg/L (S.E.M. 0.2). The mean penetration was 54% (S.E.M. 6.1). Cefpodoxime was undetectable in biopsies from two patients. The majority of serum and biopsy concentrations were in excess of the MIC90S for Haemophilus influenzae and Streptococcus pneumoniae. Cefpodoxime proxetil may be worthy of further study in clinical trials in patients with respiratory infections.

Administration, Oral↗
PubMed1992

Bronchoalveolar distribution of cefuroxime axetil and in-vitro efficacy of observed concentrations against respiratory pathogens.

The concentrations of cefuroxime in human alveolar macrophages (AM), epithelial lining fluid (ELF), bronchial mucosal biopsies and serum were measured after a single dose, equivalent to 500 mg of cefuroxime base, given in the form of the orally-administered pro-drug, cefuroxime axetil. Fourteen patients undergoing fibreoptic bronchoscopy with bronchoalveolar lavage were studied. The mean ELF concentration was 0.7 mg/L, that of bronchial biopsies was 1.8 mg/kg and that of serum 3.5 mg/L. AM-associated cefuroxime was detected in nine patients. To assess the in-vitro activity of the concentrations achieved at the potential sites of infection, clinical isolates of common respiratory pathogens were exposed to two concentrations of cefuroxime, based on the observed concentrations in ELF and bronchial mucosa. ELF and mucosal site concentrations were effective against Streptococcus pneumoniae (except one strain with reduced susceptibility to benzyl penicillin) and Haemophilus influenzae. The ELF concentration was less effective against Moraxella catarrhalis.

Aged↗
PubMed1992

Quantitative morphology and water distribution of bronchial biopsy samples.

BACKGROUND: An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial biopsy specimens consist of more than one tissue type and that drugs are often not distributed evenly. The morphology of bronchial biopsy specimens and the distribution of water between the extracellular and the intracellular compartments is therefore important. METHODS: Fifteen subjects undergoing fibreoptic bronchoscopy each had four bronchial biopsy samples taken. Thirty sections from 10 patients were examined and the proportion of tissue types noted, a morphometric analysis computer being used. The water distribution was investigated in the other biopsy specimens with radiolabelled markers. RESULTS: There was pronounced variation in the relative proportions of tissue types. Ciliated epithelium occupied a mean of 22.3% of the biopsy sample, submucosa 53.4%, muscle 17.6%, and glandular tissue 7.0%. There were no differences between second and the fourth generation subcarinae and macroscopic normality of the mucosa was a good predictor of histological normality. The extracellular water content was 40% of the total weight of the specimen and the total water content was 70%. CONCLUSIONS: These data provide the basis for pharmacokinetic study of drugs in bronchial mucosa. They show for pharmacokinetic study that macroscopically normal mucosa may be assumed to be histologically normal; that multiple biopsy specimens should be taken for any study, as there is considerable variation in the proportion of tissue types; that specimens from second and fourth generation subcarinae are the same; and that extracellular water contributes 40% to the total weight of the biopsy specimen.

Biopsy↗
PubMed1992

The distribution of temafloxacin in bronchial epithelial lining fluid, alveolar macrophages and bronchial mucosa.

The concentrations of temafloxacin, a new fluoroquinolone antimicrobial, in the potential sites of pulmonary infection were assessed by fibreoptic bronchoscopy with bronchoalveolar lavage. Fourteen patients received a course of temafloxacin, 600 mg twice daily, for three days prior to sampling. The mean serum concentration was 9.6 (SEM 1.2) mg.l-1, compared with 14.9(SEM 1.8) mg.kg-1 for bronchial mucosa, 26.5 (SEM 3.6) mg.l-1 for epithelial lining fluid and 83.0 (SEM 11.5) mg.l-1 for alveolar macrophage. In the ten patients who completed the protocol, site concentrations correlated well with serum concentrations. Temafloxacin was concentrated in each of the potential sites of infection examined and is, therefore, a promising new agent for the treatment of respiratory tract infection.

Anti-Infective Agents↗
PubMed1991

The penetration of cefpirome into the potential sites of pulmonary infection.

The concentrations of cefpirome, a new semi-synthetic cephalosporin, in the bronchial mucosa and serum were assessed after a single 1 g intravenous dose in 37 patients. Bronchoalveolar lavage allowed epithelial lining fluid (ELF) concentrations to be measured in eight subjects. The mean concentration for serum was 34.5 mg/L (S.E.M. 3.3), for bronchial mucosa 19.3 mg/kg (S.E.M. 1.9) and for ELF 7.2 mg/L (S.E.M. 1.1). The progressive reduction in cefpirome concentration in serum compared to that in bronchial mucosa and ELF is consistent with the permeability characteristics of beta-lactam antimicrobials and the barriers to movement of antimicrobial agents present in the lung.

Adult↗
PubMed1991

Comparative pharmacokinetic disposition of fluoroquinolones in the lung.

The problems associated with the study of the penetration of quinolones into the respiratory tract are discussed. New techniques allow the study of the penetration of these agents into bronchial mucosa, alveolar macrophages and epithelial lining fluid. In general quinolones are concentrated in bronchial mucosa approximately 1.5 times compared with serum. In alveolar macrophages, the agents are concentrated 14- to 18-fold compared with serum and the ratio of alveolar macrophage levels to those in epithelial lining fluid are 7.7 to 5.7:1. The concentrations of temafloxacin and ciprofloxacin in these sites suggests that these agents will be efficacious in the therapy of respiratory infections caused by Streptococcus pneumoniae.

Administration, Oral↗
PubMed1991

Microlavage: a technique for determining the volume of epithelial lining fluid.

A new technique ("microlavage") was used to determine the volume of epithelial lining fluid recovered by bronchoalveolar lavage. A standard bronchial brush tube is used to lavage a peripheral lung subsegment rapidly with 20 ml of normal saline and the concentrations of urea and total protein are measured in the aspirated fluid. Using a very short dwell time for fluid (less than 20 seconds), this technique allows the urea dilution method to be used to quantify the epithelial lining fluid protein concentration, which is then used as an endogenous marker of the epithelial lining fluid in conventional bronchoalveolar lavage fluid. The reproducibility of the calculation of the concentration of the lining fluid protein was assessed in 10 patients by performing the method in three separate lung subsegments. The mean coefficient of variation of the urea to protein ratio was 9.0%. A comparison of microlavage and conventional lavage was made in a further 28 patients. The differential cell counts were similar by the two methods, suggesting that similar epithelial lining fluid was sampled. The application of the microlavage technique to the calculation of epithelial lining fluid volume gave a lower value than the urea dilution method in association with conventional lavage. Microlavage should provide more accurate quantification of epithelial lining fluid volume and could be used in conjunction with conventional lavage, which is still required for an adequate harvest of alveolar cells.

Aged↗
PubMed1990

Concentrations of temafloxacin in serum and bronchial mucosa.

The bronchial mucosal concentrations of temafloxacin hydrochloride were determined in specimens obtained at fibreoptic bronchoscopy and compared with simultaneous serum concentrations. The 18 patients studied were given an oral dose of 400 mg b.i.d for three days to achieve steady state levels. The mean serum concentration was 6.9 mg/l (SD 2.5 mg/l) and the mean bronchial mucosal concentration 12.2 mg/kg (SD 4 mg/kg). The mucosal levels exceeded those required to inhibit most of the common respiratory pathogens, including Streptococcus pneumoniae and Pseudomonas aeruginosa. These data support the use of temafloxacin for therapy of bronchial infections.

4-Quinolones↗
PubMed1990

The effects of chronic obstructive airways disease on the ability to drive and to use a roadside alcolmeter.

Subjects with chronic obstructive airways disease may have difficulty with the roadside alcolmeter. Twenty-six subjects with a FEV1/FVC less than 60% were asked to use an alcolmeter simulator. Only ten were able to produce the necessary flow rate of 28 l min-1 for a minimum of 2.7 s, two could produce the same total volume (1.25 l) at 10 l min-1 for 7.5 s, five could only expel 10 l min-1 for 4.5 s, and nine were unable to trigger the alcolmeter at even these very low flow rates. Subjects with an FEV1 of less than 1.51 or FEV1% predicted less than 50% were very unlikely to be able to activate the alcolmeter. Ten healthy subjects were investigated to assess the accuracy of the roadside alcolmeter at a flow rate of 10 l min-1 compared to 40 l min-1. No significant difference was found in breath alcohol levels between the two flow rates. It is proposed that some modification could be made to the roadside alcolmeter, without affecting its accuracy, to allow some subjects with chronic obstructive lung disease to activate the device. A postal survey of 284 subjects with a FEV1/FVC less than 60% was carried out. Of those who were drivers or exdrivers, 24.7% had had to stop or reduce their driving because of their respiratory disease. This group had a significantly lower FEV1% predicted (P = 0.035) than those whose driving was unaffected.

Adult↗
PubMed1990

Cefepime concentrations in bronchial mucosa and serum following a single 2 gram intravenous dose.

The concentrations of cefepime in bronchial mucosa were measured after intravenous administration of a single 2 g dose in 20 patients undergoing diagnostic fibreoptic bronchoscopy. These concentrations were compared with simultaneous serum concentrations. The mean bronchial mucosal concentration was 24.1 mg/kg (s.d. 17.8 mg/kg) and the mean serum concentration was 40.4 mg/l (s.d. 28.1 mg/l). The mean percentage penetration was 59.8% (s.d. 12.5%). We conclude that a twice daily dosing of cefepime would be adequate for most respiratory infections although an 8-hourly dose may be necessary in pseudomonal infections.

Biological Assay↗
PubMed1990

Concentrations of oral lomefloxacin in serum and bronchial mucosa.

The bronchial mucosal concentrations of lomefloxacin were determined for specimens obtained by fiber-optic bronchoscopy and compared with simultaneous concentrations in serum. The 23 patients studied were given an oral dose of 400 mg once daily for 4 days to achieve steady-state levels. The median concentration in serum was 2.5 micrograms/ml (range, 1.0 to 5 micrograms/ml), and the median bronchial mucosal concentration was 5.0 micrograms/g (range, 0.7 to 18.6 micrograms/g). The median percent penetration was 177% (range, 69 to 541%). The concentrations in serum and mucosa exceeded the MIC for 90% of strains of organisms causing bronchial infections but not sufficiently to recommend lomefloxacin for the routine treatment of pneumococcal infections.

4-Quinolones↗
PubMed1990

Azithromycin concentrations at the sites of pulmonary infection.

Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.

Azithromycin↗