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Biomedical subjects

F Vallée

Publications and source records attributed to F Vallée.

At least 37 records · Page 2Linked to original sources
PubMed1995

Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses.

The pharmacokinetics and suction-induced blister fluid penetration of cefdinir following single oral administrations of 200, 300, 400, and 600 mg were studied in 16 healthy young male volunteers according to a Latin square design. Plasma, blister, and urine samples were assayed by high-pressure liquid chromatography. We observed a nonlinear relationship (P = 0.02) between the dose and the maximum concentration in plasma as well as between the dose and the area under the concentration-time curve (AUC) in plasma (P < 0.001), which may be indicative of a limited absorption process. This resulted in a lower AUC value than expected as well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg. Renal clearance decreased with increasing doses (P < 0.006; analysis of variance with the Latin square design and Games-Howell procedure). Maximal cefdinir concentrations in blister fluid were delayed compared with concentrations in plasma. Blister fluid penetration measured by the ratio of the AUC in blister fluid to the AUC in plasma was extensive (92.4 to 108.4%). Cefdinir concentrations in blister fluid remained equal to or higher than the concentrations in plasma from 6 to 12 h following cefdinir administration. On the basis of the concentrations in blister fluid and the in vitro MIC data, we estimated that cefdinir at 200 to 400 mg administered twice daily would be adequate to treat uncomplicated skin infections caused by Streptococcus pyogenes. Seven volunteers experienced episodes of light-to-moderate diarrhea. These adverse events occurred irrespective of dose.

Adult↗
PubMed1994

Characterization, crystallization and preliminary X-ray crystallographic analysis of the complex between barley alpha-amylase and the bifunctional alpha-amylase/subtilisin inhibitor from barley seeds.

The complex between a member of the barley malt alpha-amylase isozyme 2 family (AMY2-2), and the endogenous bifunctional alpha-amylase/subtilisin inhibitor, BASI, has been crystallized by the hanging drop vapour diffusion technique at a AMY2-2: BASI molar ratio of 1:1. Crystals have been grown within 4 days from solutions containing polyethylene glycol and calcium chloride. Analysis of single crystals by gel electrophoresis showed the presence of both proteins in the crystal lattice. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions a = 74.5 A, b = 96.9 A, c = 171.3 A and they diffract to 2.0 A resolution. The presence of two molecules of the 1:1 complex in the asymmetric unit gives a solvent content of 45% by volume. The 1:1 stoichiometry of the complex was confirmed by the molecular replacement method, using as a search model the recently determined three-dimensional structure of the barley alpha-amylase.

Crystallization↗
PubMed1994

Optimizing sedation following major vascular surgery: a double-blind study of midazolam administered by continuous infusion.

A randomized, double-blind study was undertaken to determine the dose requirements, recovery characteristics, and pharmacokinetic variables of midazolam given by continuous infusion for sedation in patients following abdominal aortic surgery. Thirty subjects, 50-75 yr, scheduled to undergo aortic reconstructive surgery, entered the study. Following a nitrous oxide-isoflurane-opioid anaesthetic technique, patients were randomly allocated to receive one of three loading doses (0.03, 0.06 or 0.1 mg.kg-1) and initial infusion rates (0.5, 1.0 or 1.5 micrograms.kg-1.min-1) of midazolam, corresponding to groups low (L), moderate (M) and high (H). The infusion of midazolam was adjusted to maintain sedation levels of "3, 4 or 5," which permitted eye opening in response to either verbal command or a light shoulder tap, using a seven-point scale ranging from "0" (awake, agitated) to "6" (asleep, non-responsive). Additionally morphine was given in increments of 2.0 mg iv prn for analgesia. On the morning after surgery, midazolam was discontinued, and the tracheas were extubated when patients were awake. Blood samples were taken during, and at increasing intervals for 48 hr following discontinuation of the infusion, and analyzed by gas chromatography. The desired level of sedation was maintained during more than 94% of the infusion period in all three groups, with a maximum of three dose adjustments per patient, for treatment which lasted 16.3 +/- 0.6 hr. There was, however, an increase in both the infusion rates and mean plasma concentrations from Group L to Group H (P < 0.05), which corresponded to an inverse relationship of morphine requirements during the period of sedation (P < 0.05, Group H vs Group L). Optimal midazolam infusion rates and resulting plasma concentrations at the times the infusions were discontinued (in parentheses) were as follows-Group L: 0.60 +/- 0.18 microgram.kg-1.min-1 (76 +/- 32 ng.mL-1), Group M: 0.90 +/- 0.52 microgram.kg-1.min-1 (133 +/- 71 ng.mL-1), and Group H: 1.34 +/- 0.69 microgram.kg-1.min-1 (206 +/- 106 ng.mL-1). Times to awakening were longer in Group H: 3.1 +/- 3.4 hr, than in Group L: 1.1 +/- 0.8 h, P < 0.05. Pharmacokinetic variables were found to be dose-independent over the range of infusion rates. Mean values were t1/2 beta = 4.4 +/- 1.5 hr, CL = 5.94 +/- 1.69 mL.min-1.kg-1, Vd = 3.13 +/- 1.07 L.kg-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1993

Observations on a dermatophilosis outbreak in Brahman cattle in Guadeloupe. Description, epidemiological and economical aspects.

A severe outbreak of dermatophilosis occurred in 1985 in a herd of Brahman cows imported from Martinique in Guadeloupe in July 1983. Little was known on this disease in Guadeloupe until then, for the local zebu breed is naturally highly resistant to diseases transmitted by ticks or associated with them. Conditions of appearance and development of the disease were studied in relation with herd management, climate and treatments applied. There was no evidence of the disease during the first 6 months following the importation, in a feedlot management. The first lesions of dermatophilosis appeared about 2 months after the animals were allowed to graze on pastures infested with ticks. Then, thirty percent of the herd became infected. Development of the infection increased dramatically as the humid season approached, and all the 29 Brahman cows showed lesions in July 1985. Only drastic treatments, including antibiotics and local disinfection, associated with the removal from pastures into covered stables allowed the recovery from the disease. Nevertheless, the disease caused the death of 13 head. Differences in individual reactions were also noted, and 7 different types of evolution were identified. These observations provided informations about the epidemiology of dermatophilosis in the climatic conditions of Caribbean humid tropics. They showed the economic importance of this severe disease for cattle in the region and the sensitivity of exotic breeds.

Actinomycetales Infections↗
PubMed1993

Epidemiological studies on dermatophilosis in the Caribbean.

Dermatophilosis is one of the most important diseases of domestic ruminants in the Caribbean islands where the clinical disease has been shown to be associated with the presence of the tick Amblyomma variegatum. Seroepidemiological studies were conducted to clarify the epidemiology of the disease in the region with a particular attention paid to the role of A. variegatum. A bank of 1300 cattle sera from the Lesser Antilles was screened by ELISA for the presence of antibodies to Dermatophilus congolensis. It appeared that seropositive animals do exist in islands non infested by A. variegatum and where dermatophilosis is never or seldom seen. Moreover, there was no significant difference in prevalence of seropositive animals between tick-infested and non infested areas of Martinique and Saint Lucia, 2 islands partly infested by the tick, and where dermatophilosis is only seen in tick-infested areas. Prevalence was low in small islands with a dry climate. This confirms experimental data showing that A. variegatum is not necessary for the transmission of D. congolensis which is widespread in most of the islands. High concentrations of prostaglandin E2 (between 151 and 377 ng/ml) and prostacyclin (between 124 and 134 ng/ml) found in the saliva of females A. variegatum strongly suggest that the tick could favour the development of the lesions through an immunomodulating activity of its saliva. However, despite some success in reproducing dermatophilosis on goats simultaneously infested with adult A. variegatum and scarified with Dermatophilus, no difference was observed between naturally resistant Creole cattle and very susceptible Brahman animals using the same model. The lesions of dermatophilosis remained very mild on animals of both breeds.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinomycetales Infections↗
PubMed1992

Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin.

We compared the pharmacokinetics and the serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. Fifteen healthy volunteers received 1 g of cefpirome, ceftazidime, and ceftriaxone intravenously, 500 mg of imipenem-cilastatin intravenously, and 500 mg of ciprofloxacin orally. High-performance liquid chromatographic assays were used to quantitate unchanged antibiotic in plasma and urine. Serum bactericidal activities were determined against six clinical isolates each of Staphylococcus aureus, Enterobacter cloacae, and Pseudomonas aeruginosa by using a modified microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977). Overall, cefpirome exhibited pharmacokinetics similar to those of ceftazidime: half-life (t1/2), 1.95 h; concentration at 1 h (C1h), 47 to 49 micrograms/ml for both antibiotics. Ceftriaxone displayed the longest t1/2 (7.65 h) and the highest C1h (137.8 micrograms/ml), while we observed the shortest t1/2 (1.05 h) and the lowest C1h (19.85 micrograms/ml) with imipenem. At 1 h, cefpirome and, even more so, imipenem showed significantly better serum bactericidal activities against S. aureus (1:273 and 1:80) than did the other antibiotics (P less than 0.0005; analysis of variance with randomized block design and Bonferroni correction). Against E. cloacae, we observed the highest serum bactericidal titers at 1 h with cefpirome, and this superiority vis-à-vis the other antibiotics tested was maintained for up to 8 h after dosing. Ceftazidime remained the most active agent tested against P. aeruginosa (serum bactericidal activity titers, 1:43 at 1 h) up to 8 h. In summary, the study showed that cefpirome and imipenem provide more potent serum bactericidal activities than do broad-spectrum cephalosporins against S. aureus; thus, both of these antibiotics should be adequate against serious S. aureus infections. In addition, cefpirome appears to be a promising alternative for treatment of infections caused by E. cloacae and P. aeruginosa.

Adult↗
PubMed1991

Comparative study of pharmacokinetics and serum bactericidal activity of ceftizoxime and cefotaxime.

Single 2-g intravenous doses of ceftizoxime (CZX) and cefotaxime (CTX) were given over 30 min to 10 adult volunteers in a crossover manner on two separate occasions. Concentrations of CZX, CTX, and the primary metabolite of CTX, desacetylcefotaxime (dCTX), in serum, suction-induced-blister fluid, and urine were determined by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by using an extended least-squares modeling program (MKMODEL). CZX exhibited a half-life in serum (2.05 h) longer than that of CTX (1.43 h) but comparable to that of dCTX (2.02 h). The percentage of penetration in blister fluid, estimated by area under the curve ratios, was significantly higher for CZX (164.4%) than for CTX (60.8%). Serum bactericidal activity, determined for volunteer samples at 1, 6, 8, and 12 h after patients were dosed, against clinical isolates of the Bacteroides fragilis group, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Morganella morganii were significantly higher for CZX than those for CTX against members of the family Enterobacteriaceae at all times. Serum bactericidal titers against B. fragilis were also higher for CZX than for CTX at 1 h postinfusion. Neither CZX nor CTX exhibited any bactericidal activity at any other time against the B. fragilis group. In conclusion, the serum bactericidal activity of CZX was greater and more-prolonged than that of CTX against tested strains in spite of the in vitro synergistic contribution of dCTX to CTX, equal serum elimination half-lives of dCTX and CZX, and similar antibacterial activity and similar instability under microbiological testing for CZX and CTX.

Adult↗
PubMed1990

Altered disposition of fleroxacin in patients with cystic fibrosis.

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 less than 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 less than 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.

Administration, Oral↗
PubMed1990

Tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis.

This study was designed to evaluate the tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis. Serum, peritoneal fluid, bile, gallbladder wall and pancreatic tissue concentrations of cefotaxime in these groups of pigs exceeded the MIC90 for susceptible species of Gram-negative aerobic bacteria. Cefotaxime penetration into pancreatic tissue and peritoneal fluid was increased from 2% to 2.6% and 73% to 89%, respectively, in pigs with pancreatitis in comparison with normal pigs. These increases however, were not statistically significant.

Animals↗
PubMed1990

Influence of lomefloxacin on the pharmacokinetics of theophylline.

The effect of multiple doses of lomefloxacin (400 mg twice a day) on the clearance of theophylline and the urinary excretion of its metabolites was investigated in 15 healthy male subjects. Concentrations of theophylline in plasma were measured by TDx (Abbott Diagnostics, Mississauga, Ontario, Canada). Urinary excretion of theophylline and its three major metabolites and lomefloxacin in plasma were assayed by high-performance liquid chromatography. Total theophylline clearance remained unchanged before lomefloxacin treatment and after lomefloxacin single- and multiple-dose treatments (58.02, 56.57, 54.07 ml/min, respectively). The urinary recovery of unchanged theophylline and its major metabolites stayed stable during the study. We conclude that lomefloxacin can be added to the list of fluoroquinolones that can be administered safely with theophylline.

4-Quinolones↗
PubMed1988

Pharmacokinetics of carumonam after single and multiple 1- and 2-g dosage regimens.

The pharmacokinetics of carumonam after single and multiple intravenous administration of 1- and 2-g dosage regimens were studied in 12 young male volunteers. Plasma and urine samples were collected in serial order for 24 h and assayed by high-pressure liquid chromatography. The mean elimination half-life of carumonam was not significantly affected by either dosage regimen or single dose versus steady state, ranging from 1.3 to 1.5 h. Mean concentrations at the end of the interval were not influenced by a multiple-dose administration. The normalized volume of distribution was independent of the dose, with values ranging from 0.16 to 0.19 liters/kg. After multiple administration, carumonam was cleared from the body more rapidly: from 96.2 to 121.7 ml/min after 1 g every 8 h, and from 102.1 to 122.3 ml/min after 2 g every 8 h (P less than 0.05). After 24 h, 75.0 to 80.7% of the dose was excreted unchanged in the urine. The protein binding of carumonam to human plasma remained stable at 28%. Carumonam was well tolerated by the volunteers.

Adolescent↗