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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 145 records · Page 8Linked to original sources
PubMed1996

Pharmacokinetics and penetration into inflammatory fluid of trovafloxacin (CP-99,219).

A single 200-mg oral dose of trovafloxacin (CP-99,219) was given to each of eight healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 36 h. The mean maximum concentration observed in plasma was 2.9 micrograms/ml at a mean time of 0.75 h postdose. The mean maximum concentration observed in inflammatory fluid was 1.2 micrograms/ml at 4.0 h postdose. The mean elimination half-life in plasma was 7.8 h. The overall penetration into inflammatory fluid was 64%, as assessed by determining the ratio of the area under the concentration-time curves. Recovery of the dose in urine within the first 36 h postdose was 5.0% of the administered dose. Our results indicate that trovafloxacin, at a dosage of 200 mg once or twice daily, should be adequate for the treatment of systemic infections caused by most common bacterial pathogens.

Adolescent↗
PubMed1996

In vitro activity of the tricyclic beta-lactam GV104326.

GV104326 is a novel tricyclic beta-lactam (a trinem or, formerly, tribactam). The in vitro activity of GV104326 was compared with those of cefuroxime, cefixime, amoxicillin, amoxicillin-clavulanic acid, cefpirome, and ciprofloxacin. GV104326 had in vitro activity generally similar to that of cefixime against members of the family Enterobacteriaceae (MIC at which 90% of the isolates are inhibited [MIC90], < or = 2 micrograms/ml), with cefuroxime and amoxicillin-clavulanic acid being 8- to 32-fold less active and with cefpirome being 4- to 8-fold more active against members of this family. The trinem had no activity against Pseudomonas aeruginosa or Stenotrophomonas maltophilia (MIC90, > 128 micrograms/ml) but was the most active agent against Acinetobacter calcoaceticus. GV104326 was particularly active against gram-positive cocci. Ninety percent of methicillin-susceptible Staphylococcus aureus strains were susceptible to 0.03 microgram of GV104326 per ml, making it the most active agent studied. Enterococci and Lancefield group A and B streptococci were generally equally or somewhat more susceptible to GV104326 than they were to amoxicillin. Streptococcus pneumoniae strains were highly susceptible to GV104326, and those strains which showed decreased susceptibility to penicillin were generally twofold more susceptible to the trinem than to amoxicillin. Haemophilus influenzae and Moraxella catarrhalis were highly susceptible to GV104326 (MIC90s, 0.12 and 0.03 microgram/ml, respectively). The anaerobes Clostridium perfringens, Bacteroides fragilis, and Peptostreptococcus spp. were more susceptible to the trinems (formerly tribactams) than to the other agents studied.

Amoxicillin↗
PubMed1996

Tissue penetration of the fourth generation parenteral cephalosporins.

In this review, the methods employed to study tissue penetration are discussed. Mathematical, animal and human models all have their positive and negative features, however studies in man must be central to studying the pharmacokinetics of these agents. The newly introduced parenteral cephalosporins (cefpirome, cefepime and cefoselis) have been studied in man. In general they penetrate tissues to similar extents to other beta-lactam agents. Non-specialised tissues such as inflammatory exudate and peritoneal fluid are rapidly and extensively penetrated. More specialised tissues (such as prostate) are penetrated to a moderate extent (30 to 50%). Certain sites - such as the CSF - are poorly penetrated (c. 5 to 10%). It is important to have a knowledge of this information prior to therapeutic trials of such agents.

Animals↗
PubMed1995

Relationship between elevated lipid peroxides, vitamin E deficiency and hypertension in preeclampsia.

Preeclampsia or pregnancy-induced hypertension is a major cause of both maternal and fetal-neonatal morbidity and mortality. The deficiency of vitamin E can cause accumulation of lipid peroxidation products, which, in turn, can induce vasoconstriction. This study has examined any evidence of increased cellular lipid peroxidation and accumulation of malonydialdehyde (MDA, an end product of lipid peroxidation) in pregnancy-induced hypertension and any relationship between the elevated MDA and lower vitamin E levels with hypertension in pregnant women. EDTA-Blood was collected from pregnant women at the time of delivery. Plasma vitamin E was determined by HPLC; MDA by the thiobarbituric acid-reactivity. Subjects with diastolic blood pressure (DBP) > or = 90 mm Hg were considered hypertensive (HT) and with < 90 mm Hg normotensive (NT). Data (Mean +/- SE) from 49 NT and 11 HT women show that HT has significantly lower vitamin E (22 +/- 1 vs 27 +/- 1 nmole/ml, p < 0.03) and elevated MDA levels (0.56 +/- 0.06 vs 0.43 +/- 0.02 nmole/ml, p < 0.03) compared to NT; the ages and gestational ages of women were similar. Among all women, there was a significant positive relationship between DBP and MDA levels (r = 0.27, p < 0.05), and a significant negative relationship between vitamin E levels and DBP (-0.36, p < 0.005), and a significant negative relationship between MDA and vitamin E levels (r = 0.27, p < 0.05). Thus, HT women's plasma has significantly lower E and higher MDA levels, and DBP significantly correlates with the extent of vitamin E deficiency and increased MDA levels. This study suggests a relationship between elevated lipid peroxidation and lower vitamin E levels and hypertension in pregnancy (preeclampsia).

Adult↗
PubMed1995

Latency period after preterm premature rupture of membranes: a comparison of ampicillin with and without sulbactam.

OBJECTIVE: To compare ampicillin with and without sulbactam with respect to the effect on the latency period after preterm premature rupture of membranes (PROM). METHODS: Patients with PROM at 25-35 weeks' gestation were offered participation in a randomized blinded trial comparing ampicillin-sulbactam with ampicillin. Evaluations for cervical pathogens were performed on admission and patients were followed-up with daily maternal and fetal evaluation. Maternal and neonatal outcomes were analyzed using indicated techniques. RESULTS: Fifty-three women were studied, with 25 receiving ampicillin-sulbactam and 28 receiving ampicillin. The ampicillin-sulbactam group had a significantly longer latency period (433 +/- 625 versus 143 +/- 165 hours, P = .03) and significantly fewer neonatal complications (five versus 20, P < .001). Although no neonatal infectious complications were observed in sulbactam-treated cases, there were four cases of neonatal sepsis and two of neonatal pneumonia in the ampicillin group. Also, significantly more neonates in the ampicillin group required prolonged oxygen and ventilatory support. There was no significant difference in maternal morbidity. CONCLUSIONS: In our population with preterm PROM, a broad-spectrum antibiotic that provides anaerobic coverage appears to extend latency and decrease neonatal morbidity without increasing adverse maternal outcome.

Adult↗
PubMed1995

Concentrations of OPC-17116, a new fluoroquinolone antibacterial, in serum and lung compartments.

The efficacy of an antibiotic is usually predicted from serum concentration and MICs for likely pathogens, but in the lung, tissue concentrations may be more relevant. This study compares concentrations of a new fluoroquinolone, OPC-17116, in serum, epithelial lining fluid (ELF), alveolar macrophages and bronchial mucosa, in 24 adults. OPC-17116 400 mg was given daily for 4 days, and diagnostic bronchoscopy was performed up to 13 h after the final dose. Mucosal biopsies were taken from macroscopically normal sites, alveolar macrophages were harvested by lavage, and ELF volume was derived from urea concentrations in bronchial lavage fluid and blood. A microbiological assay, using Escherichia coli, was used to assay OPC-17116 concentration in serum, bronchial mucosa, ELF and alveolar macrophages. The mean concentration of OPC-17116 in serum was 1.2 mg/L. Serum concentrations were significantly exceeded in bronchial mucosa (mean ratio 3.13) in ELF (mean ratio 12.21) and in macrophages (mean ratio 194.52). Penetrations of these compartments considerably exceeded those reported for other fluoroquinolones, and concentrations in all tissues were substantially higher than previously reported MIC90 levels for a variety of bacteria, including Streptococcus pneumoniae. A clinical role for OPC-17116 is suggested in a wide range of respiratory infections, including those due to intracellular bacteria.

Adult↗
PubMed1995

The in-vitro activity of CP 99,219, a new naphthyridone antimicrobial agent: a comparison with fluoroquinolone agents.

The in-vitro activity of a new fluoroquinolone, CP 99,219 was compared with that of ciprofloxacin, DU 6859, sparfloxacin and levofloxacin. CP 99,219 showed generally similar in-vitro activity to the other compounds tested against the Enterobacteriaceae (MIC90 of all agents < 0.5 mg/L except Morganella morganii). It was found to be more active than ciprofloxacin, sparfloxacin and levofloxacin against the strains of Acinetobacter calcoaceticus tested (MIC90 1 mg/L). CP 99,219 was found to be four-fold more active against strains of Stenotrophomonas maltophilia than ciprofloxacin (MIC90 1 and 8 mg/L, respectively). Haemophilus influenzae and Neisseria spp. were highly susceptible to all the agents tested. CP 99,219 was more active than ciprofloxacin, sparfloxacin and levofloxacin against Gram-positive organisms, but less active than DU 6859. The enhanced anti-Gram-positive activity of CP 99,219 was most marked against the nine strains of methicillin-resistant Staphylococcus aureus tested. The MIC90 of CP 99,219 of these strains was 1.0 mg/L compared with 64 mg/L for ciprofloxacin. Against Bacteroides fragilis, CP 99,219 (MIC90 0.25 mg/L) and DU 6859 (MIC90 0.03 mg/L) were more active than the other quinolones. Chlamydia spp. were susceptible to < or = 0.12 mg/L of CP 99,219. Mycobacterial strains tested were less susceptible to CP 99,219 than to ciprofloxacin. The protein binding of CP 99,219 was 87.9% at 1 mg/L.

4-Quinolones↗
PubMed1995

In-vitro activity of two glycylcyclines against enterococci resistant to other agents.

Two new glycylcyclines, CL 329,998 and CL 331,002, were tested for in-vitro activity against 178 clinical strains of enterococci which were resistant to one or more of the commonly used agents (ampicillin, high level gentamicin, vancomycin and teicoplanin). Both glycylcyclines demonstrated good activity (MICs < or = 0.5 mg/L) against all isolates tested, including those strains which demonstrated multiple resistance. As resistant enterococci are increasing in importance, new agents with activity against these strains are urgently required. Glycylcyclines have in-vitro activity which suggests they may be useful agents for treatment of infections caused by these organisms.

Anti-Bacterial Agents↗
PubMed1995

Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid.

Two levofloxacin administration regimens were used for six healthy male volunteers. They received either 500 mg of levofloxacin orally every 12 h for five doses or 500 mg every 24 h for three doses, and then 6 weeks later they received the other course. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured with a microbiological assay following administration of the final dose. Mean peak concentrations in plasma of 9.3 and 6.6 micrograms/ml were attained 1.1 and 1.2 h after the 12- and 24-h regimens, respectively. Mean peak concentrations is inflammatory fluid of 6.8 and 4.3 micrograms/ml were attained at 2.3 and 3.7 h, respectively. The average steady-state concentrations were 5.0 and 2.2 micrograms/ml in plasma and 4.7 and 2.3 micrograms/ml in inflammatory fluid, respectively. The mean terminal elimination half-lives for plasma were 7.9 and 8.0 h for the two regimens, respectively, and the same values were noted for inflammatory fluid. The overall penetration into inflammatory fluid ranged from 88 to 101% with the 12-h regimen and 83 to 112% with the 24-h regimen. Mean urinary recoveries were 87 and 86% over the corresponding interval of the 12- and 24-h regimens, respectively. These results suggest that administration of levofloxacin once and twice daily should be efficacious for infections caused by the majority of pathogens.

Adolescent↗
PubMed1995

Pharmacokinetics and tissue penetration of the new fluoroquinolone grepafloxacin.

A single 400-mg oral dose of grepafloxacin (OPC-17116) was given to each of six healthy male volunteers, and the concentrations of the drug in plasma, cantharides-induced inflammatory fluid, and urine were measured over the subsequent 12 h. The mean peak concentration in plasma of 1.5 micrograms/ml was attained at a mean time of 2.0 h postdose. The mean peak concentration in inflammatory fluid of 1.1 micrograms/ml was attained at a mean time of 4.8 h postdose. The mean elimination half-life in plasma was 5.2 h, and that in inflammatory fluid was 12.7 h. The overall penetration into inflammatory fluid was 180.6% (or 133% if one aberrant result from one volunteer is excluded). Recovery of the drug in urine during the first 24 h postdose was 8.3% of the administered dose. Our results indicate that a once- or twice-daily dosage of grepafloxacin should be adequate to treat systemic infections caused by most bacterial pathogens.

Adult↗