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M LeBel

Publications and source records attributed to M LeBel.

48 records · Page 3Linked to original sources
PubMed1985

Serum bactericidal activity of ceftazidime increased by netilmicin.

Cephalosporins are often used in combination with aminoglycoside antibiotics in the treatment of gram-negative infections. Although ceftazidime possesses activity against gram-negative bacteria, especially against Pseudomonas, combined use with aminoglycosides is useful. In this study, 12 healthy volunteers (6 men, 6 women; mean age 21.5 yr) received a single dose of ceftazidime 1 g iv and one week later ceftazidime 1 g iv with netilmicin 100 mg iv. Both antibiotics were infused over five minutes. Concentrations of ceftazidime were determined by high performance liquid chromatography. Serum bactericidal activity (SBA) was evaluated against seven microorganisms isolated from clinical specimens. The mean peak serum level of ceftazidime was 113.4 micrograms/ml. At eight hours, we observed a concentration of 2.6 micrograms/ml. The total clearance was 126 ml/min, while the renal clearance was 100 ml/min. Ceftazidime exhibited a half-life of 1.9 hours. Up to ten hours, the SBA of ceftazidime against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, and Salmonella typhi was greater than 1:8 in more than 90 percent of samples. At one hour, ceftazidime exhibited a SBA of 1:4 for Staphylococcus aureus, and 1:16 for Pseudomonas aeruginosa. With the addition of netilmicin, median SBA against Staph. aureus and P. aeruginosa were 1:32 and 1:64, respectively, at one hour. Netilmicin enhanced the SBA of ceftazidime. The combination was not effective against Streptococcus faecalis.

Adult↗
PubMed1983

Effect of probenecid on the pharmacokinetics of ceftizoxime.

The effect of probenecid on the pharmacokinetics of ceftizoxime was studied. Twelve healthy male volunteers first received 1 g of ceftizoxime either by iv rapid injection or by im injection. One week later, each subject was again given a similar dose of ceftizoxime, one hour after the ingestion of 1 g of probenecid. Serum and urinary concentrations were determined by a HPLC method. Ceftizoxime half-life was increased by probenecid from 1.7 to 2.3 h in the iv group, and 1.9 to 2.8 h in the im group (P less than 0.05, paired t-test). Probenecid increased the area under the serum concentration-time curve by 49% in both groups. There was no significant change in the volume of distribution following probenecid. This study confirms that ceftizoxime is eliminated by glomerular filtration and tubular secretion and that the latter is inhibited by probenecid.

Adult↗
PubMed1983

Lack of interference of five new beta-lactam antibiotics with serum creatinine determination.

Several cephalosporins falsely elevate creatinine concentration as determined by the Jaffé reaction. We studied the in vitro effect of various concentrations of cefoperazone, ceftizoxime, ceftriaxone, ceftazidime, and azthreonam on the creatinine determination in serum, using both a manual and an automated technique. No false elevation or change in baseline creatinine concentration could be observed with any of the five antibiotics. With the use of large concentrations in serum of these beta-lactam antibiotics, we can estimate their lack of interference with creatinine determination in urine as well. Therefore, there is no need to relate the timing of blood (and urine) sampling for creatinine assay to dosage of these antibiotics.

Anti-Bacterial Agents↗
PubMed1983

Antihypertensive effect of indapamide with special emphasis on renal prostaglandin production.

A study was undertaken in 19 patients with benign to moderate essential hypertension to verify the effect of indapamide alone or combined with a beta-blocker on plasma renin activity, plasma aldosterone, serum potassium and urinary prostaglandins PGE2 and PGF2a. Blood pressure was normalized in 11 (58%) patients with 2.5 mg indapamide/day. In the remaining 8 patients, the addition of pindolol resulted in blood pressure control. Under indapamide, a 70% increase in plasma renin activity and 81% (p less than 0.01) in plasma aldosterone was observed, whereas there was an 18% (p less than 0.001) decrease in potassium. Simultaneously, an increase in urinary PGE2 and PGF2a was observed; these values were significant for PGE2 (p less than 0.025). The addition of pindolol did not produce significant change in the biochemical parameters measured. The increase in the excretion rate of primary prostaglandins could play a role in the mode of action of indapamide.

Adult↗
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

Effect of ten new beta-lactam antibiotics on urine glucose test methods.

The effect of ten new beta-lactam antibiotics (cefoperazone, cefotaxime and its metabolite desacetylcefotaxime, ceftazidime, ceftizoxime, ceftriaxone, aztreonam, azlocillin, mezlocillin, piperacillin, and ticarcillin) on the accuracy of Clinitest, Diastix, and Tes Tape determinations of glycosuria was investigated. Solutions of each of the antibiotics were prepared in urine over a range of clinically obtainable drug concentrations. Urine samples from a healthy subject were used to prepare simulated diabetic urine by adding dextrose to achieve concentrations of 0.5%, 1%, and 2%. With penicillin derivatives, falsely elevated Clinitest readings generally were observed at lower glucose concentrations. When no glucose was present, cephalosporins and the monobactam, aztreonam, gave a dark green-black color that could only be interpreted as 0% on the Clinitest color chart. At higher urine glucose concentrations (1% and 2%), no interaction with Clinitest could be demonstrated, with the exception of a few falsely reduced readings. All urine solutions containing beta-lactam antibiotics were estimated accurately by both Diastix and Tes Tape. The unpredictability of the Clinitest-beta-lactam antibiotics interaction should discourage the use of this urine glucose test in patients who receive these drugs. The glucose-oxidase tests, Diastix and Tes Tape, may be used as qualitative tests for glycosuria in patients treated with beta-lactam antibiotics.

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↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of ranitidine and famotidine in healthy elderly subjects: a double-blind, placebo-controlled comparison.

The pharmacokinetics and pharmacodynamics of ranitidine and famotidine were studied in 13 healthy elderly volunteers. On 3 mornings separated by a 1-week wash-out period, each subject received a single oral dose of ranitidine 300 mg, famotidine 40 mg, and placebo in a crossover, randomized fashion with double-dummy administration. Plasma and urine concentrations of ranitidine and famotidine were determined by high-performance liquid chromatography. Intragastric pH was measured for 24-hours with an antimony probe. Famotidine's plasma half-life (4.42 hrs) was significantly longer than ranitidine's (3.14 hrs, p < 0.05, paired t test). The 24-hour, area under the curve of pH profiles of the two drugs were significantly different from placebo (p < 0.05, analysis of variance and Fisher PLSD test) but not from each other. The duration of effect (defined as median pH > 4) was similar for ranitidine and famotidine, 10.3 and 9.9 hours, respectively (p = 0.713, paired Student's t test). Thus both agents exhibited a similar duration of 24-hour antisecretory response under these study conditions.

Aged↗
PubMedDate not supplied

The effect of timing of a standard meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic agent ziprasidone.

STUDY OBJECTIVE: To evaluate the influence of a high-fat meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic drug ziprasidone. DESIGN: Open, randomized, three-way crossover study. SETTING: University-based research facility. SUBJECTS: Eight healthy male volunteers. INTERVENTIONS: Ziprasidone 20 mg was administered under fasting conditions (treatment A), and directly after (treatment B) and 2 hours after (treatment C) a standard high-fat breakfast. MEASUREMENTS AND MAIN RESULTS: Serial blood samples were obtained over 36 hours. Three objective psychometric tests were employed to evaluate daytime vigilance at baseline and 2 hours after each dose. Ziprasidone had a significant effect on area under the curve (AUC0-infinity), maximum serum concentration, and half-life (analysis of variance all p<0.05), with the mean AUC0-infinity being significantly greater (627.2 +/- 206.4 vs 371.0 +/- 126.5 ng x hr/ml, ANOVA with Bonferroni's criteria p<0.016) and half-life significantly shorter (4.7 +/- 0.8 vs 6.6 +/- 1.3 hrs, ANOVA with Bonferroni's criteria p<0.016) after treatment B compared with treatment A. Although similar trends were observed after treatment C compared with treatment A, the differences did not reach statistical significance when Bonferroni's correction criteria were applied (p>0.016). CONCLUSION: These data suggest an increase in systemic exposure to the highly lipophilic compound ziprasidone when taken after fatty foods, possibly due to improved drug dissolution and solubilization. The drug's longer half-life under fasting conditions may reflect dissolution-limited absorption, although this could not be directly assessed. Despite postprandial increases in ziprasidone AUC0-infinity and maximum concentration, daytime vigilance was not affected.

Adolescent↗