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Biomedical subjects

C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 19 recordsLinked to original sources
PubMed1992

Lomefloxacin concentrations in bone after a single oral dose.

We studied the penetration characteristics of lomefloxacin in bone in 30 patients with osteoarthritis undergoing total hip replacement. Patients were given a single oral 400 mg dose at various times from 1 to 12 hours prior to removal of bone samples. The peak plasma and bone (subchondral bone from femoral head) concentrations reached approximately 4.0 micrograms/mL at 2 hours post-dose and 3.0 micrograms/mL at 3 hours post-dose, respectively. At 12 hours post-dose both plasma and bone concentrations were still greater than 1.0 microgram/mL. Two hours after dosing the average bone-to-plasma ratio was greater than 0.6. These data indicate that a single 400 mg oral dose of lomefloxacin attains bone concentrations that are above its usual minimum inhibitory concentrations for susceptible organisms.

Administration, Oral↗
PubMed1992

Effect of sucralfate on pharmacokinetics of fleroxacin in healthy volunteers.

The effect of sucralfate on the pharmacokinetics of fleroxacin was assessed in 20 healthy male volunteers. The study was of a two-way crossover design in which subjects were randomized to one of the following two regimens at the time of entry: (i) a single 400-mg dose of fleroxacin alone or (ii) a 400-mg dose of fleroxacin given once and 1 g of sucralfate given every 6 h starting 24 h before fleroxacin treatment and continuing for 48 h after fleroxacin treatment. Blood samples were collected immediately before fleroxacin administration and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 h postdosing. Fleroxacin concentrations in plasma and urine were determined by high-performance liquid chromatography. While concurrent of fleroxacin and sucralfate resulted in a decrease in the area under the plasma concentration-time curve, a decrease in the maximum concentration, and an increase in the time to the maximum concentration (P < 0.05), these changes were modest compared with the interaction of other quinolones with sucralfate. The relative bioavailability of fleroxacin given with sucralfate, calculated from the area under the concentration-time curve, was 76% compared with that of fleroxacin alone. This is significantly better than the bioavailabilities of other quinolones (1.8 to 12.3%) when they are administered with sucralfate.

Adult↗
PubMed1992

Intraocular penetration of rifampin in humans.

The penetration of rifampin into human aqueous humor was determined in 15 patients undergoing elective cataract surgery. Between 0.9 and 5.5 h after administration of a single 600-mg oral dose, concentrations ranged from 6.0 to 21.5 mg/liter in serum and from less than 0.2 to 1.3 mg/liter in aqueous humor.

Administration, Oral↗
PubMed1992

The relative bioavailability of temafloxacin administered through a nasogastric tube with and without enteral feeding.

The relative bioavailability of a single oral dose of temafloxacin given with and without enteral feeding was determined in 18 healthy male volunteers in a randomised crossover study. Subjects were administered 600mg of temafloxacin orally as an intact tablet, or a crushed tablet suspended in water administered through a nasogastric tube with or without an enteral feeding solution [Osmolite (Ross) 100 ml/h started 2h before administration of temafloxacin and continued for 4h postdose]. Plasma samples were analysed by a high performance liquid chromatographic technique. Mean peak plasma concentrations (Cmax) for the oral tablet, crushed tablet, and crushed tablet with enteral feeding solution were 3.95 +/- 1.02, 4.85 +/- 0.69, and 4.69 +/- 0.61 mg/L/70kg, respectively, and mean calculated area under the concentration-time curve from time 0 to 48h (AUC(0-48h)) values were 48.1 +/- 11.0, 54.5 +/- 6.52, and 49.7 +/- 5.89 mg/L.h/70kg, respectively. In terms of AUC(0-48h) and Cmax, the relative bioavailability of temafloxacin after nasogastric delivery of crushed temafloxacin given with and without an enteral feeding solution was equivalent to the reference oral regimen.

Administration, Oral↗
PubMed1992

Considerations in dosage selection for third generation cephalosporins.

Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients. Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding. Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site. Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment. Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations. The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors.

Acute Kidney Injury↗
PubMed1992

Ofloxacin vs ciprofloxacin: a comparison.

Ofloxacin and ciprofloxacin are fluoroquinolones with similar characteristics. However, important differences can be observed in their antimicrobial activity, clinical utility, and pharmacokinetic and interaction profiles. Ofloxacin is more active in urethral chlamydia infections; it also may more effectively eradicate staphylococcal infections and Streptococcus pneumoniae pulmonary infections. Furthermore, ofloxacin does not significantly alter theophylline concentrations. Ciprofloxacin has better activity against gram-negative bacilli, an advantage which may be negated by ofloxacin's longer half-life and higher serum levels. Therefore, while both drugs are effective as treatment of infections due to gram-negative organisms, ofloxacin is also appropriate in the treatment of: 1) infections where both aerobic gram-negative rods and staphylococci or S. pneumoniae are documented or suspected, 2) urethritis, particularly when C. trachomatis is documented or suspected, 3) infections in patients concomitantly receiving theophylline.

Bacterial Infections↗
PubMed1991

Quantification of in-vitro post-antibiotic effect based on the mean recovery-time. I: Theoretical perspectives and a practical procedure.

An empirical description of the post-antibiotic effect has been previously proposed on the basis of the time required for the bacterial density to increase by one log10 following antimicrobial exposure. In this study, a set of theoretical perspectives are established and the post-antibiotic effect quantitatively defined based on the mean-recovery time. The mean recovery-time can be determined by measuring the area above the growth curve of a bacterial population following antimicrobial exposure. It can be shown that the previously proposed description of the post-antibiotic effect may be regarded as a special case of the definition based on the mean-recovery. Furthermore, a practical procedure is described for the quantitation of the post-antibiotic effect from a given set of data in the form of a growth curve.

Anti-Bacterial Agents↗
PubMed1991

Quantification of in-vitro post-antibiotic effect based on the mean recovery-time. II: A comparison of colony counting versus photometric methods for the determination of bacterial growth.

In the preceding paper, a method for the quantification of the post-antibiotic effect (PAE) has been developed based upon the mean recovery-time of an antibiotic-treated bacterial population, showing that the mean recovery-time is determined by the area above a growth curve of the bacterial population. Such an area determination of PAE implies that this method is less likely to be influenced by the early portion of a growth curve and therefore less dependent on the ability of a technique to detect a minimum bacterial density (sensitivity limit). In this study, this implication is further demonstrated in theory and through experimentation. As a result, an approach to estimation of contribution of the early portion of a growth curve to the quantitation of PAE based on the mean recovery-time is derived. The PAE of ciprofloxacin on Escherichia coli ATCC 25922 was determined under different test conditions using colony count and optical density measurements for determining bacterial growth. Differences in durations of the PAE quantitated by the mean recovery-time from the colony count measured and optical density measured growth curves were not statistically significant (P greater than 0.05).

Anti-Bacterial Agents↗
PubMed1979

Penetration of cephapirin and cephalothin into the right atrial appendage and pericardial fluid of patients undergoing open-heart surgery.

To prevent infection in 27 patients who underwent coronary artery bypass or cardiac valve replacement surgery, each patient received a single 2-g dose of either cephalothin or cephapirin intravenously before the operation (prior to opening of the chest cavity). Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various intervals after injection of the antibiotic and were assayed for cephalosporin concentrations. Cephapirin consistently reached higher levels than cephalothin in the right atrial appendage and pericardial fluid; both cephalosporins, however, reach concentrations in these sites well above their minimal inhibitory concentrations (MICs) for penicillin-resistant staphylococci. Of particular interest was the brevity of the period (about 100 min) during which levels of both antibiotics were maintained above the MIC in the right atrial appendage. This finding emphasizes the need for administration of these antibiotics shortly before surgery.

Adult↗
PubMed1978

Physiological perfusion model for cephalosporin antibiotics I: Model selection based on blood drug concentrations.

Various cephalosporins with different degrees of protein binding were administered to human volunteers. Blood samples were collected as a function of time and were assayed for drug content by a microbiological assay. A pharmacokinetic analysis of the data was performed using a two-compartment model with and without protein binding in the central compartment and a perfusion model. Both the two-compartment model without protein binding and the physiological perfusion model adequately described the blood levels of all three cephalosporins.

Blood Proteins↗
PubMed1978

Pharmacokinetics of oral cephalosporins: cephradine cephalexin.

A crossover experiment was utilized to compare the pharmacokinetics of a 1-g dose of cephalexin tablets, cephalexin capsules, or cephradine capsules in nine normal human volunteers. These antibiotics were administered as three formulations: two 500-mg capsulin every 6 hr for five doses, and one 1000-mg tablet of cephalexin every 6 hr for five doses. Pharmacokinetic parameters in the experimental groups showed no statistical differences (p greater than 0.1), indicating that these drugs are equivalent pharmacokinetically.

Administration, Oral↗
PubMed1978

Evaluation of an oral prolonged-release antibiotic formulation.

The antibiotic cephalexin was formulated as an oral prolonged-release tablet and evaluated by in vitro dissolution testing as well as in vivo in 10 human subjects. Comparisons were made of the time course of the blood levels among the prolonged-release formulation, the commercially available capsule, and intravenous administration. Even though lower peak blood levels were attained in the prolonged-release tablet, absorption continued for at least 6 hr. Comparison with in vitro dissolution data showed that absorption was dissolution rate limited. Bioavailability comparisons showed that the prolonged-release formulation was completely available, as was the commercial oral capsule.

Administration, Oral↗
PubMed1978

Cefazolin.

After 5 years of use, cefazolin can be considered similar to cephalothin as a therapeutic agent and in its potential for adverse reactions. When cefazolin and cephalothin are compared by appropriately designed clinical trials, neither cefazolin's slightly greater in-vitro susceptibility to staphylococcal beta-lactamase inactivation, nor its slightly greater microbiologic activity for some enterobacteraciae has been shown to result in any readily apparent therapeutic differences. The important differences between cefazolin and cephalothin--and this is also probably true with respect to cephapirin and cephradine--are not in therapeutic effectiveness, microbiologic activity, or toxicity but rather in pharmacokinetics and cost-effectiveness.

Agranulocytosis↗
PubMed1977

Rapid sensitive fluorometric analysis of cephalosporin antibiotics.

A rapid and sensitive fluorometric analysis for cephalosporins, which can also be applied to penicillins, is presented. The method involves reaction with 0.1 N sodium hydroxide at 100 degrees, producing stable fluorescent products. This method was applied to cephalexin and ampicillin with detection at concentrations as low as 0.01 mug/ml.

Ampicillin↗