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Dive into the research topics where François Vallée is active.

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Featured researches published by François Vallée.


Clinical Pharmacology & Therapeutics | 1996

The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin

Bettina A. Hamelin; Jacques Turgeon; François Vallée; Pierre-Maxime Bélanger; Francois Paquet; Marc LeBel

Substrates and inhibitors of the cytochrome P450 isozyme CYP2D6 have overlapping structural characteristics. Two prototype serotonin uptake inhibitors, sertraline and fluoxetine, share these structural criteria and have been identified as potent inhibitors of CYP2D6 in vitro. The current study was undertaken to investigate whether genetically determined CYP2D6 activity alters the disposition of sertraline or fluoxetine or both.


The Journal of Clinical Pharmacology | 1998

Effects of Rifabutin and Rifampicin on the Pharmacokinetics of Ethinylestradiol and Norethindrone

Marc LeBel; Eric Masson; Edith Guilbert; Dave Colborn; Francois Paquet; Sylvie Allard; François Vallée; Prem K. Narang

This open‐label, randomized, three‐way crossover study of 28 healthy premenopausal women was conducted to compare the impact of concomitant rifabutin and rifampicin on the safety, pharmacokinetics, and pharmacodynamics of the oral contraceptives ethinylestradiol and norethindrone (Ortho‐Novum 1/35; Ortho Pharmaceutical, Raritan, NJ). Each participant received oral contraceptives daily for 21 days for the first control cycle, then was randomized to one of two sequences to receive oral contraceptives with concomitant rifampicin and rifabutin at equal doses of 300 mg/day for 10 days. Ethinylestradiol, norethindrone, follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, rifampicin, and rifabutin (and metabolite) were measured in plasma over the same time frames in all three cycles. Safety was assessed from before the beginning to the end of each cycle. Twenty‐two subjects completed all three cycles. Compared with the control cycle, rifabutin and rifampicin significantly altered the disposition of the oral contraceptive. Area under the concentration—time curve from 0 to 24 hours (AUC0–24) and maximum plasma concentration (Cmax) of ethinylestradiol decreased by 64% and 42%, respectively, after coadministration with rifampicin and by 35% and 20%, respectively, after coadministration with rifabutin. The AUC0–24 of norethindrone decreased by 60% and 20% after coadministration with rifampicin and rifabutin, respectively. Unlike progesterone levels, FSH and LH levels increased during coadministration with rifampicin and rifabutin. The incidence of spotting was significantly higher after coadministration with rifampicin (36.4%) and rifabutin (21.7%) than during the control cycle (3.7%). Although both rifampicin and rifabutin affected the pharmacokinetics of ethinylestradiol and norethindrone, the magnitude of this effect was more pronounced with rifampicin. Likewise, the fact that the highest incidence of spotting occurred with rifampicin was consistent with higher metabolic induction by rifampicin. Despite the fact that there was no change in progesterone levels, it is recommended that patients be advised to use additional contraceptive methods while receiving rifabutin or rifampicin with oral contraceptives to prevent inadvertent pregnancy.


Pharmacotherapy | 1986

Pharmacokinetics of Ciprofloxacin in Elderly Subjects

Marc LeBel; Gilles Barbeau; Michel G. Bergeron; Denis Roy; François Vallée

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 μg/ml for the younger group (p < 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 < 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.


Therapeutic Drug Monitoring | 1986

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

François Vallée; Marc LeBel; Michel G. Bergeron

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.


Journal of Chromatography B: Biomedical Sciences and Applications | 1987

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

D Croteau; François Vallée; Michel G. Bergeron; Marc LeBel

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.


Clinical Pharmacology & Therapeutics | 1990

Altered disposition of fleroxacin in patients with cystic fibrosis

Joëlle Mimeault; François Vallée; Robert Seelmann; Fritz Sörgel; Michel Ruel; Marc LeBel

Thirteen patients with cystic fibrosis and 12 healthy control volunteers received a single oral 800 mg dose of fleroxacin and 800 mg every day for 5 days. Interstitial fluid penetration was studied by the suction‐induced blister technique. Fleroxacin and its two major metabolites, N‐demethyl and N‐oxide, were analyzed in plasma and urine by HPLC. Single‐dose absorption parameters (absorption rate constant, normalized peak plasma drug concentration, and time to reach peak concentration) and total urinary excretion indicated that fleroxacin was absorbed more slowly and more completely in patients with cystic fibrosis than in control subjects. Fleroxacin volume of distribution tended to be smaller in patients with cystic fibrosis and it reached statistical significance after a single dose when normalization for lean body mass was applied. When normalized for lean body mass, the formation clearance of N‐demethyl fleroxacin and N‐oxide fleroxacin was significantly greater in patients with cystic fibrosis than in control subjects (p < 0.05). These data concur with those of others showing an induction of drug‐metabolizing enzymes in cystic fibrosis. Renal clearances of fleroxacin and its metabolites were significantly increased in cystic fibrosis (p < 0.05), and this seems to be explained by a decreased tubular reabsorption of these compounds. The differences seen in the pharmacokinetics of fleroxacin in cystic fibrosis support the theories of generalized induction of drug metabolism and of a defective renal tubular reabsorptive process of drugs in cystic fibrosis.


Therapeutic Drug Monitoring | 1986

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

Céline Fiset; François Vallée; Marc LeBel; Michel G. Bergeron

Summary: 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 suppliers 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 μg/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 > 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.


Pharmacotherapy | 1993

Cefepime Pharmacokinetics in Cystic Fibrosis

Bettina A. Hamelin; Nathalie Moore; Catherine A. Knupp; Michel Ruel; François Vallée; Marc LeBel

Study Objective. To determine the disposition of cefepime in patients with cystic fibrosis compared with healthy controls.


Clinical Pharmacology & Therapeutics | 1996

Role of CYP2D6 in the Demethylation of Fluoxetine In Vivo

Bettina A. Hamelin; Jacques Turgeon; François Vallée; Pierre-Maxime Bélanger; Francois Paquet; Marcel Lebel

Clinical Pharmacology & Therapeutics (1996) 59, 137–137; doi: 10.1038/sj.clpt.1996.48


Clinical Pharmacology & Therapeutics | 2003

Pharmacokinetics of sibutramine in healthy subjects under fasting fed conditions

Zohreh Abolfathi; François Vallée; Eric Masson

Clinical Pharmacology & Therapeutics (2003) 73, P65–P65; doi:

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