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F Vallée

Publications and source records attributed to F Vallée.

45 records · Page 3Linked to original sources
PubMed1987

High-performance liquid chromatographic assay of erythromycin and its esters using electrochemical detection.

A high-performance liquid chromatographic analysis of erythromycin and its esters in plasma, urine and saliva is presented. A diethyl ether extract of sample was chromatographed on a reversed-phase column and components of the column effluent were monitored by electrochemical detection at +0.9 V (vs. Ag/AgCl). The method sensitivity limit was 10 ng with inter-day coefficients of variation from 3.2 to 10.3%. In order to assess precisely the relative concentrations of erythromycin esters (ethylsuccinate or estolate) and their active by-product erythromycin base, it is necessary to adopt measures preventing their continuous hydrolysis in biological fluids and during sample preparation.

Chromatography, High Pressure Liquid↗
PubMed1986

Determination of ciprofloxacin in biological samples by reversed-phase high performance liquid chromatography.

Previously reported high performance liquid chromatography (HPLC) assays for ciprofloxacin have used cumbersome fluorescence detection. UV absorbance is more commonly used for assay of antibiotics. Separation of ciprofloxacin and nalidixic acid (internal standard) was achieved using UV absorption at 313 nm, and a reversed phase C-18 Nova-Pak column. The mobile phase consisted of 35% phosphate buffers adjusted to pH 7.4, 65% methanol, and 5.5 mM hexadecyltrimethylammonium bromide. Retention times were 4.3 and 7.3 min, respectively, for ciprofloxacin and nalidixic acid. Serum sample preparation involved protein precipitation with acetonitrile (1:2), followed by methylene chloride and 2-propanol extraction (90:10). After evaporation, reconstitution with a minimal volume of mobile phase allowed for 5X concentration of the sample. The sensitivity limit of the assay was 0.06 microgram/ml. The response was linear from 0.125 to 10.0 micrograms/ml (r greater than 0.999). The coefficient of variation for day-to-day analysis was less than 5.3%, and the recovery was 55%. When compared with microbiological assay in serum, the correlation coefficient was 0.922 (n = 58). This HPLC method using UV detection provided comparable results to those obtained by fluorimetry. Data from three pharmacokinetic studies showed this method to be reliable and accurate.

Biological Assay↗
PubMed1986

Comparative study of serum bactericidal activity of cefotaxime alone or in combination with tobramycin.

The objectives of this study were to investigate the bactericidal activity in serum of cefotaxime alone or in combination with tobramycin against clinical strains and to determine the influence of tobramycin on the pharmacokinetics of cefotaxime. The peak bactericidal activity in serum of cefotaxime alone against Klebsiella oxytoca, Enterobacter aerogenes, Serratia marcescens, Pseudomonas cepacia, and Listeria monocytogenes varied between 1:4 and 1:256. Bactericidal activity could still be detected at 6 h against K. oxytoca and L. monocytogenes. The addition of tobramycin increased the bactericidal activity of cefotaxime against E. aerogenes from 1:16 to 1:128 (P less than 0.01). Cefotaxime recovery from urine was significantly decreased when tobramycin was added. Our data are comparable with those of other investigators who have shown a limited increase in the bactericidal activity of cefotaxime when aminoglycosides are added.

Adult↗
PubMed1986

Tissue penetration of ciprofloxacin after single and multiple doses.

The pharmacokinetics and the suction-induced blister fluid penetration of ciprofloxacin were compared after a single dose (500 mg) and after multiple dosing (500 mg q8h for 13 doses). Significantly higher peak levels of ciprofloxacin in serum were observed after multiple dosing (3.51 versus 2.26 micrograms/ml; P less than 0.01). Increased elimination half-life occurred after multiple dosing; this seems to be mostly related to decreased systemic clearance secondary to a diminished nonrenal clearance (240.0 versus 125.0 ml/min). Ciprofloxacin appeared rapidly in the blister fluid, and the percentage of penetration (AUC0-tBF/AUC0-t serum) yielded values of 88.8 versus 84.7% after single and multiple doses, respectively. Ciprofloxacin levels in serum and blister fluid at the end of the dosing interval (8 h) were superior or almost superior to MICs for sensitive organisms including Pseudomonas aeruginosa. Comparative studies of ciprofloxacin metabolite excretion after multiple doses in healthy subjects and in renal insufficiency patients are needed.

Absorption↗
PubMed1986

Pharmacokinetics and pharmacodynamics of ciprofloxacin in cystic fibrosis patients.

The pharmacokinetics and blister fluid penetration of oral ciprofloxacin were compared in 11 cystic fibrosis (CF) patients who had sputum colonization but were asymptomatic and in 12 healthy volunteers after a single dose (500 mg) and at steady state (500 mg every 8 h). The antibacterial effect of ciprofloxacin therapy was also evaluated by bacterial counts of colonizing pathogens in the respiratory secretions of CF patients. The CF patients were 15.9% lighter in weight than the controls (P less than 0.05). After a single dose, the elimination half-life of ciprofloxacin was decreased by a third in the CF patients as compared with the controls (2.62 versus 3.93 h, respectively; P less than 0.01). This was the result of a diminished apparent volume of distribution in CF subjects. Interestingly, we observed no statistically significant difference in total apparent and renal clearances between the groups. Suction-induced blister fluid penetration was not different between CF patients and healthy volunteers. In CF patients, ciprofloxacin exhibited levels in respiratory secretions above the reported MIC for Pseudomonas aeruginosa: 1.36 and 1.86 micrograms/ml at 2 h after a single dose and at steady state, respectively. An important fall (mean, 3.9 log10/ml) in the log titer in 10 patients with P. aeruginosa in their respiratory secretions was observed after 5 days of treatment. However, this improvement was short-lived; the secondary increase in bacterial counts observed in five patients and the development of five resistant strains were causes for concern. The pharmacokinetic results presented here showed that ciprofloxacin should be administered every 8 or even every 6 h in CF patients.

Adult↗
PubMed1986

Protein binding of ceftriaxone: comparison of three techniques of determination and the effect of 2-hydroxybenzoylglycine, a drug-binding inhibitor in uremia.

Ceftriaxone is a third-generation cephalosporin exhibiting a long half-life and a concentration-dependent protein binding. This study compared three techniques of protein binding determination (equilibrium dialysis chamber, ultrafiltration cones (Centriflo), and ultrafiltration (Centrifree micro-partition system) on human plasma and serum at ceftriaxone concentrations achieved clinically. A second objective was to determine the effect of 2-hydroxybenzoylglycine (HBG) on the protein binding of ceftriaxone. High performance liquid chromatography (HPLC) and liquid scintillation counting assays were used. Equilibrium dialysis was rotated for 12 h. The supplier's recommendations were followed for ultrafiltration techniques. The plasma protein binding of ceftriaxone, as determined by equilibrium dialysis and assayed by HPLC, decreased from 98.6 to 73.5% for drug concentrations varying from 25 to 400 micrograms/ml. Somewhat lower values were obtained with Centrifree, the binding fell from 92.1 to 73.5% for the same concentration range. Serum protein binding was similar to results obtained with plasma samples. Centriflo cones yielded more inconsistent results. A significant difference was seen between the three techniques (p less than 0.0001, three-way analysis of variance). The addition of HBG, a compound that inhibits drug binding in uremia, resulted in ceftriaxone binding defects similar to those seen in uremic serum. Although equilibrium dialysis remains a classic method of protein binding determination, Centrifree appears to be a better system.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics of ciprofloxacin in elderly subjects.

The pharmacokinetics of single-dose oral ciprofloxacin 500 mg was ascertained in 12 elderly and 12 young subjects. Mean age of the elderly volunteers was 75.4 years and the mean measured creatinine clearance in this group was 40.7 ml/min. Serum and saliva were collected in serial order for 24 hours (elderly) and 10 hours (young), and assayed for ciprofloxacin by high-performance liquid chromatography. The geriatric subjects had higher serum levels throughout the sampling period, with a peak level of 3.24 +/- 0.79 versus 2.26 +/- 0.75 micrograms/ml for the younger group (p less than 0.005; one-way analysis of variance). A twofold increase in the ciprofloxacin half-life may be partly explained by a decrease in the glomerular filtration rate, as shown by slower ciprofloxacin renal clearance (152.4 +/- 54.2 vs 395.6 +/- 139.0 for elderly and young subjects respectively; p less than 0.001). We concluded that in elderly patients, ciprofloxacin should be administered at an interval not less than every 12 hours to prevent accumulation and eventually toxicity.

Adult↗
PubMedDate not supplied

Cefepime pharmacokinetics in cystic fibrosis.

STUDY OBJECTIVE: To determine the disposition of cefepime in patients with cystic fibrosis compared with healthy controls. DESIGN: Open-label, single-dose study. SETTING: Laboratoire de Pharmacocinétique Clinique, Université Laval, Québec, Canada. PATIENTS AND SUBJECTS: Twelve patients with the confirmed diagnosis of cystic fibrosis (CF) and 12 healthy volunteers. One subject with CF withdrew for personal reasons; the data of another patient were excluded from the evaluation of renal values due to incomplete urine collection. INTERVENTIONS: A single 2000-mg dose of cefepime was administered as a 30-minute intravenous infusion. Healthy subjects did not use any other drugs throughout the study. Those with CF refrained from taking prophylactic antibiotics prior to and during the study, but continued to use pancreatic enzymes, multivitamins, and beta-agonist and/or steroid inhalers. One patient continued insulin treatment. MEASUREMENTS AND MAIN RESULTS: Cefepime's maximum concentration was approximately 150 micrograms/ml at the end of the infusion, half-life 2-2.5 hours, and urinary recovery 80% in both groups. No statistically significant difference was seen in any of the pharmacokinetic values between the groups, except for the mean residence time (2.03 +/- 0.26 vs 2.39 +/- 0.37 hrs; p < 0.02). Total clearance was 19% higher in patients with CF than in healthy volunteers (119.7 +/- 20.1 vs 103.5 +/- 19.8 ml/min), perhaps due to higher renal (95.1 +/- 12.4 vs 85.1 +/- 12.0 ml/min) and/or nonrenal (25.4 +/- 13.1 vs 18.4 +/- 12.0 ml/min) clearances in subjects with CF. CONCLUSIONS: The disposition of cefepime is not significantly affected by CF, and dosage adjustment appears not to be necessary in these patients.

Adolescent↗