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C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 127 records · Page 7Linked to original sources
PubMed1993

Overview of the pharmacokinetics of fleroxacin.

The pharmacokinetic properties of fleroxacin in relation to other quinolones are presented. Fleroxacin, like all quinolones, is well absorbed, reaching peak concentrations within 2 hours. Interactions with Ca2+ and Al3+ are minimal and possibly of little clinical importance. The drug is eliminated via filtration in the kidney. It is therefore sensitive to changes in renal function. Accumulation of drug in the body is minimal, and change from intravenous to oral dosing results in nearly identical serum concentrations. Aside from the modest effect of metals on its absorption, fleroxacin does not interact/compete with substances oxidized in the liver, such as theophylline, and drug interactions are minimal. Its long serum half-life (8-12 hours) allows once-a-day dosing. This feature, along with its modest drug interactions, makes fleroxacin an attractive quinolone, at least with respect to its pharmacokinetics.

Absorption↗
PubMed1993

Evaluation of the efficacy of ciprofloxacin against Streptococcus pneumoniae by using a mouse protection model.

A mouse protection model was used to investigate the association of the pharmacokinetics and pharmacodynamics with the in vivo efficacy of ciprofloxacin compared with that of penicillin G in the treatment of mice infected with Streptococcus pneumoniae ATCC 6303. Mice were inoculated intraperitoneally with 10 times the minimum lethal dose of S. pneumoniae. For determination of the 50% protective dose, subcutaneous antibiotics were begun 1 h after infection and were continued for 24 h. The 50% protective doses of ciprofloxacin and penicillin G were 25.52 +/- 1.95 and 0.307 +/- 0.006 mg/kg of body weight, respectively, an 83-fold difference in efficacy. For 100% protection with penicillin G, the time that the drug concentration needed to remain above the MIC was 51 min, a value easily achieved in most clinical situations. For 100% protection with ciprofloxacin, the peak concentration/MIC ratio must reach a value of 10.6. This ratio is rarely achieved with this drug against S. pneumoniae in clinical practice. These pharmacodynamic differences probably contribute to the reported differences in clinical success between these agents.

Animals↗
PubMed1993

Vancomycin therapeutic drug monitoring: is it necessary?

OBJECTIVE: To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients. DATA SOURCES: A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations. DATA SYNTHESIS: The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients. CONCLUSIONS: Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients.

Animals↗
PubMed1993

Lomefloxacin clinical pharmacokinetics.

Lomefloxacin is a quinolone antibiotic with chemical and microbiological properties similar to most commercially available agents of this class. There are differences, however, between lomefloxacin and other quinolones in activity against specific micro-organisms, a situation that is typical of most antibiotic classes. The pharmacokinetics of lomefloxacin support once- or twice-daily dosage, depending on the pathogen or site of infection. This is a result of its relatively high serum concentrations and long half-life. The outstanding pharmacokinetic features of lomefloxacin are its high degree of tissue distribution, lack of significant metabolism (and, therefore, no competitive drug interactions with other metabolised drugs showing a common metabolic pathway), and good oral absorption. Like most fluoroquinolones, lomefloxacin can chelate with heavy metals. However, this interaction can be eliminated by administering lomefloxacin 2h before the cation-containing products. Dosage adjustments are required in patients with renal dysfunction. However, patients with liver disease do not require alterations in lomefloxacin dosage regimens. The safety profile, lack of significant drug interactions and convenience of administration make lomefloxacin a useful agent in specific clinical settings.

Administration, Oral↗
PubMed1993

Impact of nosocomial infections on hospital costs.

Modifications in antibiotic programs for treatment of nosocomial infections can result in significant cost savings within a hospital. Most hospitals initially treat nosocomial infections empirically, based on their epidemiologic history. Designed to be effective against a broad range of possible pathogens, this type of therapy usually includes two or more drugs administered parenterally. This is expensive because the total cost of treatment includes the cost of not only multiple drug therapy but also the materials and labor needed to prepare and administer them. "Streamlining of therapy" to a single oral or parenteral agent can usually be done once more definitive information is known about the pathogen and the patient's condition. This approach maximizes therapeutic effectiveness and reduces costs. Streamlining therapy for nosocomial infections has helped Hartford Hospital decrease the antibiotic budget from 30 to 15% of the total drug budget, resulting in annual cost savings of $150,000 to $250,000.

Anti-Bacterial Agents↗
PubMed1993

Oral ciprofloxacin, ofloxacin, and lomefloxacin as alternatives to intravenous antimicrobial therapy.

Ciprofloxacin, ofloxacin, and lomefloxacin are oral fluoroquinolones with ideal characteristics for oral antimicrobial therapy. These agents provide 1) appropriate and reliable serum concentrations, 2) broad antimicrobial activity, 3) proven efficacy in the treatment of serious infections, and 4) good tolerability. Although cations decrease the absorption of these drugs, there are proven means of avoiding these interactions. Therefore, these agents could easily be utilized as alternatives to prolonged intravenous treatment of many infectious diseases in patients who do not have conditions which impair drug absorption.

Administration, Oral↗
PubMed1993

Pharmacokinetics of minocycline and vancomycin in rabbits.

The pharmacokinetic disposition of minocycline and vancomycin was studied in New Zealand White rabbits before initiating an experimental staphylococcal endocarditis protocol. Minocycline was administered in a multiple-dose regimen of 3 mg/kg i.v. every 12 h, 3 mg/kg i.v. every 8 h, and 6 mg/kg i.v. every 8 h. Vancomycin was given in a similar fashion using regimens of 75 mg/kg i.v. every 12 h and 50 mg/kg i.v. every 8 h. Multiple serum samples were obtained after the fifth dose and drug concentrations were analyzed by microbiologic assay. The pharmacokinetic parameters for each of the drug regimens were calculated using a two-compartment model by nonlinear least-squares regression. No statistically significant differences were noted in the volume of distribution or the half-life of the individual dosing regimens for either agent. As a result of this study, it appears that a minocycline regimen of 6 mg/kg i.v. every 8 h and a vancomycin regimen of 50 mg/kg i.v. every 8 h are appropriate dosing schemes for a comparative study of these agents in rabbits.

Animals↗
PubMed1993

Use of pharmacodynamic concepts in developing a cost-effective dosing method for piperacillin.

Because they were almost always used in combination with an aminoglycoside, piperacillin and mezlocillin were considered therapeutic alternatives at Hartford Hospital, a 900-bed teaching facility. To determine an appropriate comparative dose, the bactericidal activities of 5 gm of mezlocillin and 4 gm and 3 gm of piperacillin were compared. The results demonstrated that 4 gm of piperacillin possessed stronger bactericidal activity than either 3 gm of piperacillin or 5 gm of mezlocillin. Hartford Hospital has since approved an antibiotic management program using 4 gm of piperacillin every 8 hours, thereby reducing the daily cost of antibiotic therapy. The modified program offers the hospital measurable cost savings without jeopardizing the quality of care.

Cost-Benefit Analysis↗
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↗