Search PubMed⌕ Search

Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 271 records · Page 15Linked to original sources
PubMed1990

The pharmacokinetics of the oral cephalosporins--a review.

The pharmacokinetics of the older and more recent oral cephalosporins are reviewed. With the exception of cefadroxil the older agents (cephalexin, cephradine and cefaclor) have serum elimination half-lives of less than or equal to 1 h and hence have to be administered three to four times daily. The urinary recovery of these agents is high (greater than 80% of oral dose) with the exception of cefaclor (54%). Cefaclor is also chemically unstable. The newer agents can be divided into those that are prodrugs (cefpodoxime proxetil and cefuroxime axetil) and compounds that are absorbed as such (cefixime, cefprozil and ceftibuten). They all have half-lives greater than 1.25 h and can be given once or twice daily. The penetration of these agents into an inflammatory exudate was studied and found to be cefixime 132%, ceftibuten 113%, cefpodoxime 104%, cefuroxime 92% and cefprozil 79% of the serum concentration. The penetration of cefpodoxime and cefixime into the respiratory tract was also studied; the mean percentage bronchial mucosal penetration was 52% for the former and 38% for cefixime. The urinary recovery of these newer agents (with the exception of ceftibuten) tends to be less than that of the earlier agents. There was a relationship between the serum elimination half-life of these agents and the degree of tissue penetration, those agents with longer half-lives penetrating to a greater extent.

Absorption↗
PubMed1990

Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis.

The cytolytic capacity of mycobacterial antigen-stimulated peripheral blood mononuclear cells, from healthy Mantoux-positive volunteers and from patients with tuberculosis was investigated. Polyclonal T cell lines induced by 7 days of stimulation in vitro with PPD or a sonicate of Mycobacterium tuberculosis lysed both autologous macrophages and Epstein-Barr virus (EBV) transformed B cell lines which had been pulsed with mycobacterial antigens, to a greater extent than unpulsed target cells or target cells pulsed with an irrelevant antigen (streptokinase/streptodornase). The killing of mycobacterial antigen-pulsed macrophages and EBV-transformed B cell line targets was inhibited by monoclonal antibodies to MHC class II antigens but not by antibodies directed against MHC class I antigens. PPD-pulsed EBV-transformed lymphoblastoid cell lines (LCL) competitively inhibited the killing of mycobacterial antigen-pulsed macrophages, whereas natural killer (NK) sensitive K562 cells (with or without antigen pulsing) did not inhibit mycobacterial antigen-dependent cytolysis of macrophages. Patients with tuberculosis showed a spectrum of mycobacterial antigen-induced cytolytic capacity. Those with extensive tissue necrosis (e.g. cavitatory pulmonary tuberculosis or caseous, extrathoracic tuberculosis) had high levels while patients with disseminated (miliary) tuberculosis or disease refractory to treatment showed little evidence of mycobacterial antigen induced cytotoxicity. The ability of mycobacterial antigen-stimulated lymphoblasts to kill specific antigen-pulsed autologous macrophages was not significantly different between healthy donors and patients with tuberculosis. However, the 'mycobacterial antigen-specific' component of this cytolysis was significantly deficient (P less than 0.01) in patients. We conclude that mycobacterial antigen-specific cytotoxic T cell responses may play a significant part in the immune response to mycobacterial infection.

Adult↗
PubMed1990

Pharmacokinetics and inflammatory fluid penetration of cefpodoxime proxetil in volunteers.

The pharmacokinetics of cefpodoxime were determined after a single oral dose of 261 mg of cefpodoxime proxetil, equivalent to 200 mg of cefpodoxime, was given to each of six healthy male volunteers. Concentrations in serum, urine, and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak level in plasma was 2.1 micrograms/ml, attained at a mean time of 2.9 h. The mean half-life of elimination from serum was 2.2 h. The inflammatory exudate was penetrated moderately rapidly, the mean peak level being 1.7 micrograms/ml at 3.5 h. The mean percent penetration of the inflammatory exudate was 103.7. The mean 24-h urine recovery of cefpodoxime was 32.2%. This study suggests that cefpodoxime proxetil taken once or twice daily will be sufficient to treat urinary or systemic infections caused by susceptible pathogens.

Adult↗
PubMed1990

In vitro activity of Bay v 3522, a new cephalosporin, compared with activities of other agents.

The in vitro activity of Bay v 3522, a new aminobenzothiazol cephem, was compared with those of other oral beta-lactams. Bay v 3522 displayed high activity against Staphylococcus spp. (MICs for 90% of strains tested [MIC90S], 0.5 micrograms/ml), Streptococcus pneumoniae (MIC90, 0.06 micrograms/ml), and Haemophilus influenzae and Branhamella catarrhalis (MIC90S, 2 micrograms/ml). There was limited activity against members of the family Enterobacteriaceae, with the MIC90S being between 4 and greater than 128 micrograms/ml. The stability of Bay v 3522 to hydrolysis by the SHV-1 and TEM-1 enzymes was intermediate to those of cephalexin (least hydrolyzed) and cefaclor, but it was markedly more stable than amoxicillin. There was high affinity to the chromosomally mediated P99 enzyme. The protein binding of Bay v 3522 was 45%. The primary target of Bay v 3522 was penicillin-binding protein 3.

Bacteria↗
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

Pharmacokinetics and tissue penetration of ceftibuten.

The pharmacokinetics of the cephalosporin ceftibuten were determined after the fifth and final dose of 200 mg given every 12 h. Concentrations in plasma and cantharidin-induced inflammatory fluid were determined by a microbiological assay. Samples for three volunteers were assayed by a high-performance liquid chromatographic procedure to determine levels for both cis and trans ceftibuten. The mean peak level of ceftibuten in serum was 10.9 micrograms/ml at a mean time of 1.8 h after administration, and the mean elimination half-life from plasma was 2.5 h. Penetration into the inflammatory fluid was good, the mean peak level being 9.2 micrograms/ml at a mean time of 3.7 h. The mean percent penetration into the inflammatory fluid was 113.4%. High-performance liquid chromatography analysis showed that the mean peak level of the trans isomer was 5.7% that of the cis isomer. This study suggests that twice-daily doses of ceftibuten should be sufficient to treat urinary or systemic infections caused by susceptible pathogens.

Adult↗
PubMed1990

Mechanism of action of lomefloxacin.

The inhibition of supercoiling activity of reconstituted Escherichia coli DNA gyrase by lomefloxacin, ciprofloxacin, and norfloxacin was determined. The concentrations of quinolones needed to inhibit DNA synthesis in Escherichia coli, Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were also measured. The kinetics of uptake of [14C]lomefloxacin and unlabeled lomefloxacin into whole cells of E. coli KL-16 and S. aureus NCTC 8532 and the induction of RecA in E. coli GC2241 were assayed. All strains had wild-type susceptibilities to quinolones. The concentration of quinolones needed to inhibit DNA synthesis by 50% correlated with the MIC for members of the family Enterobacteriaceae and P. aeruginosa. The concentration of quinolones needed to inhibit DNA synthesis by 50% for late-logarithmic-phase S. aureus also correlated with the MIC, unlike the data from early-logarithmic-phase cultures. E. coli and S. aureus showed a similar pattern of uptake kinetics of [14C]lomefloxacin and unlabeled lomefloxacin, indicating that the difference in the susceptibilities of the two species is probably due to different target site affinities. Essentially, lomefloxacin was less active than ciprofloxacin and ofloxacin and had activity similar to those of norfloxacin and enoxacin.

Anti-Infective Agents↗
PubMed1990

Meropenem pharmacokinetics and penetration into an inflammatory exudate.

The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem in plasma was 1.1 h, with the concentration in plasma declining from a mean of 23.6 micrograms/ml at 1 h to 0.7 micrograms/ml at 6 h. The inflammatory fluid penetration was rapid (time to maximum concentration of drug in serum, 0.75 h), and the penetration was 111%. The recovery of meropenem in urine at 24 h was 65.4% of the administered dose.

Adult↗
PubMed1990

Positive pleural pressure decreases coronary perfusion.

Pressure surrounding the heart (PSH) rises with maneuvers that increase pleural pressure. This may decrease left ventricular (LV) oxygen demand by reducing LV afterload. However, positive PSH may also directly impede coronary flow. To study the effects of positive PSH on coronary perfusion, PSH was increased in 10-mmHg increments from 0 to 60 mmHg in an isolated canine heart-lung preparation with constant venous return, arterial pressure, and lung volume. Increased PSH caused a rapid significant (P less than 0.001) fall in left atrial transmural pressure (PLATM) of up to 1.28 +/- 0.31 mmHg. With constant venous return and lung volume, this was interpreted to reflect decreased LV afterload. However, at levels of PSH greater than 30 mmHg, initial decreases in PLATM were followed by sustained increases, suggesting that there was a deterioration in cardiac function despite the lower level of afterload. Increased PSH was also associated with decreases in circumflex coronary artery flow [flow (ml/min) = 52.4 - 0.4PSH, P less than 0.01]. Moreover, when the circumflex coronary artery was maximally dilated with adenosine, the effects of PSH were amplified [flow (ml/min) = 137.9 - 1.78PSH, P less than 0.001], indicating that positive PSH mechanically impeded coronary flow. When PSH was raised to 60 mmHg for 90 s, the aortic-coronary sinus lactate concentration difference fell from 0.71 +/- 0.09 to 0.10 +/- 0.21 mM (mean +/- SE, P less than 0.001, n = 8), suggesting myocardial ischemia. We conclude that positive PSH directly decreases myocardial perfusion. This may lead to ischemic cardiac dysfunction, especially in patients with low arterial pressure or coronary artery disease.

Animals↗
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↗
PubMed1989

Tissue penetration and pharmacokinetics of lomefloxacin following multiple doses.

The pharmacokinetics of lomefloxacin were studied after three days of oral administration of 400 mg/day lomefloxacin. Following the final dose the concentrations in serum, urine and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak serum level was 4.9 mg/l at a mean time of 0.8 h. The mean serum elimination half-life was 6.2 h. The mean maximum inflammatory fluid level attained was 3.2 mg/l at 2.7 h. Urinary recovery accounted for the greater part of lomefloxacin's elimination.

4-Quinolones↗
PubMed1989

Intraperitoneal penetration of cefpirome.

Twenty-six patients undergoing elective gastrointestinal surgery received a 1 g intravenous dose of cefpirome before operation. Serum and peritoneal fluid samples, obtained 0.5-7.6 h following administration, were assayed for cefpirome by a microbiological assay. The serum half-life of cefpirome was 2.1 h. The mean concentration of cefpirome in peritoneal fluid 0-2 h after administration was 44.4 micrograms/ml. The half-life of cefpirome in peritoneal fluid was 2 h, with mean concentrations of less than 10 micrograms/ml measured 6 h after administration. The mean percentage of intraperitoneal penetration of cefpirome over the study period was 97.7%. The therapeutic implications are discussed.

Adult↗
PubMed1989

The killing action of fleroxacin upon Bacteroides fragilis.

The killing kinetics of fleroxacin against four strains of Bacteroides fragilis were investigated. Viable counts were determined from 0 to 24 h after exposure to fleroxacin at multiples of the MIC. A one to three log reduction in viable count was observed after 2 h at 8 mg/l fleroxacin, and a more rapid rate of killing was seen at greater concentrations of the antimicrobial agent. An increase in cell length was observed at concentrations at and above the MIC from 2 h after exposure. The presence of a bacteriostatic concentration of chloramphenicol had negligible influence on viability but inhibited cell elongation.

Anti-Bacterial Agents↗
PubMed1989

Cefixime, in-vitro activity, pharmacokinetics and tissue penetration.

The in-vitro activity of cefixime was studied with clinical isolates and compared with that of other agents. Cefixime exhibited good activity against the Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae, including beta-lactamase producing strains. Activity was also high against Streptococcus pneumoniae and group A and group B beta-haemolytic streptococci. Staphylococcus aureus, faecal streptococci, anaerobic bacteria and Pseudomonas aeruginosa were not susceptible. Activity against susceptible isolates was comparable to cefotaxime and was normally superior to cefuroxime, cephalexin and amoxycillin. The pharmacokinetics of cefixime were studied in six healthy male volunteers, each receiving a 400 mg oral dose following an overnight fast. Tissue penetration of the antibiotic was estimated with a cantharides-induced blister method. The mean serum elimination half-life was 3.8 h, the mean peak concentration was 3.7 mg/l. Penetration into tissue fluid was rather slow [Tmax 6.7 h) but percentage penetration was high (132.6%). Urinary excretion was low with a 24 h recovery rate of less than 20%, though the concentrations achieved in urine exceeded the MICs of most common urinary tract pathogens for up to 24 h post-dose.

Adult↗