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Biomedical subjects

D de Lauture

Publications and source records attributed to D de Lauture.

At least 19 recordsLinked to original sources
PubMed1995

The effect of intravenous phenylephrine on airway calibre in asthma.

Tracheobronchial vasoconstriction and subsequent reduction of airway wall thickness due to the alpha 1-agonist methoxamine, might be responsible for prevention of exercise-induced asthma, and reduction of bronchial hyperresponsiveness to methacholine increase in exercise performance in patients with impaired left ventricular function. Since bronchial wall oedema plays an important role in asthma, we have now investigated the bronchial response to the intravenously administered alpha 1-agonist, phenylephrine, in asthma of various severity. Increasing noncumulative intravenous phenylephrine doses (100 to 600 micrograms) were injected in 18 asthmatic subjects (three groups: mild asthma, mild asthma with recent acute attack, severe obstructive asthma) and in 11 control subjects. Changes in specific airways resistance (sRaw) on phenylephrine were linearly related to the dose administered in 16 out of 18 asthmatic subjects, and in only 3 out of 11 control subjects. In the asthmatic subjects, sRaw increased in 10 patients whose asthma was mild, or bronchial obstruction mild to moderate, and decreased in the remaining 8 asthmatic subjects with more severe disease or with a higher degree of bronchial obstruction. Changes in forced expiratory volume in one second (FEV1) were consistent with those of sRaw. In the five asthmatic subjects who underwent the protocol twice, results were reproducible. There was no difference in the responses of heart rate between the three groups of asthmatic subjects. It is likely that phenylephrine acts both via airway smooth muscle contraction, an effect which might predominate in mild asthma, and via mucosal vasoconstriction, which might overcome the effect on smooth muscle in more severe asthma with bronchial wall oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Lack of effect of phenobarbital on ex vivo leukocyte oxidative metabolism in healthy volunteers.

Oxidative metabolism in activated human polymorphonuclears catabolizes leukotriene B4 by a cytochrome P450 omega-hydroxylase and procainamide by a myeloperoxidase. The percentage of leukotriene B4 metabolized by activated human polymorphonuclears and the apparent enzymatic parameters of procainamide metabolism were studied ex vivo in six healthy volunteers before and after phenobarbital intake (100 mg/day) for 10 days and in six healthy control volunteers. No differences were found between groups for the difference in percentage of leukotriene B4 metabolized between day 11 and day 1. The apparent enzymatic parameters, Km and Vm, of procainamide oxidation did not differ significantly between the groups both on day 1 and day 11. These results do not show any evidence of inducibility of leukotriene B4 and procainamide metabolism in human polymorphonuclears. However, a positive correlation between 6 beta OH-cortisol excretion and percentage of leukotriene B4 metabolized was observed on day 11. This study suggests that human polymorphonuclears cytochrome P450 leukotriene B4 omega-hydroxylase and procainamide metabolism is not a useful method to study cytochrome P450 induction in clinical pharmacology.

17-Hydroxycorticosteroids↗
PubMed1992

Azelastine reduces allergen-induced nasal response: a clinical and rhinomanometric assessment.

The effect of azelastine 2 mg b.d. p.o. for 10 days on grass pollen-induced nasal responses in 16 patients with grass pollen allergic rhinitis has been assessed. The study was a double blind, randomized, placebo controlled, crossover trial, with a 10-14 day wash-out period. Patients were challenged with grass pollen before and after placebo and azelastine. The response was assessed by measurement of nasal resistance using active posterior rhinomanometry, by weighing nasal secretions, and by counting sneezes. The sensation of nasal obstruction was assessed with a visual analogue scale. After measurement of baseline total nasal resistance, doubling doses of allergen were sprayed into both nostrils at 15 min intervals until the nasal resistance was doubled. Cumulative doses of allergen that doubled prechallenge nasal resistance, numbers of sneezes and the amounts of nasal secretions were similar before azelastine as well as before and after placebo (cumulative dose, mean, (microgram): 2.3, 4.2 and 2.1 respectively, N.S.). After azelastine, the cumulative dose of allergen was increased (7.3 micrograms), and nasal secretions and the number of sneezes were decreased. The visual analogue scores were similar before and after azelastine as well as before and after the placebo. It is concluded that azelastine reduced the allergen-induced nasal responses.

Adult↗
PubMed1990

Establishing a phase I unit: organisation.

The organisation of a phase I unit must take into account the safety, quality and scientific requirements of such studies. The clinical pharmacology unit demands a highly qualified staff, as well as intensive care equipment. The investigator, generally a clinical pharmacologist who coordinates the different tasks as a project leader, has often to initiate a fruitful collaboration with a specialised consultant staff in order to implement the studies.

Drug Evaluation↗
PubMed1989

Pharmacokinetic interactions between theophylline and rioprostil.

The study is of double-blind crossover design. The effects of rioprostil, an analogue of prostaglandin E1, at a dose of 300 micrograms b.d., and placebo on the kinetic of slow-release theophylline are investigated. Eight healthy male volunteers participate in the study, each study period lasting for one week. During the first period, the doses of theophylline are altered in response to measured theophylline levels, 200 mg or 400 mg b.d. Regardless of placebo or rioprostil treatment, side effects appear before day 6 and are related specifically to theophylline administration. Blood samples are taken on days 4 and 5 to check steady-state plasma levels of theophylline and on days 6 and 7 to determine the main pharmacokinetic parameters. The same schedule is used for the second period of treatment. The achievement of steady-state concentration is verified. The mean pharmacokinetic parameters do not show a significant difference when slow-release theophylline is given alone or with rioprostil. These results are likely to be clinically relevant and, therefore, the theophylline dose should not be changed if rioprostil is prescribed at the same time as the theophylline.

Adult↗
PubMed1989

Treatment of duodenal ulcer with rioprostil: a randomized multicentre double-blind study.

The effectiveness of rioprostil, 300 micrograms b.d. is evaluated in evolutive duodenal ulcer in a double-blind study in five French and North African centres. A total of 115 patients are included in the study (57 in the rioprostil group and 58 in the placebo group). After a 4-week treatment period, a significantly higher endoscopic healing rate is observed in the rioprostil group (57%) compared with the placebo group (33%) (p less than 0.01). The mean time with abdominal pain is significantly lower in the rioprostil group (5.6 +/- 4.4 days) compared to the placebo group (12.7 +/- 5 days) (p less than 0.001). Clinical and biological tolerance is excellent. The only side effect is diarrhoea (3.5% in the rioprostil group). In only one case does diarrhoea necessitate cessation of treatment. Rioprostil, 300 micrograms b.d., is thus effective in the treatment of developing duodenal ulcer.

Anti-Ulcer Agents↗
PubMed1988

Gentamicin monitoring in neonates.

The elimination of gentamicin (G) was studied in 103 neonates (30 premature) during the first month of life after 2.5 mg/kg i.v. (as infusion) over 20-30 min. G plasma levels, measured by EMIT assay, were obtained before and at 1, 2, 3, and 6 h after infusion. We derived individual first-order kinetic parameters and designed optimal dose regimens. G plasma clearance, half-life, and recommended dose (mg/kg/h) changed exponentially with postnatal age during the first 14 days of life. No significant changes in kinetic values were noted during the first 3 days of life; however, they varied linearly with gestational age when they were measured during this period. Apgar score at 10 min and blood urea nitrogen significantly influenced the same parameters. The predictive value of a designed dose regimen was evaluated at steady-state, after dosage adjustment using two plasma concentration values: the minimum plasma concentration was below 2 mg/L in 93% of the patients; the plasma concentration observed within 1 h after completion of the infusion was (mean +/- SD) 5.33 +/- 0.97 mg/L. Our data suggest that 2.5 mg/kg every 12 h is appropriate in most neonates except for 0-2-day-old premature infants who require 2.5 mg/kg every 18 h. Monitoring of G plasma levels is advisable in infants with low Apgar score and/or renal failure.

Age Factors↗
PubMed1988

Cumulative dose-response curves for assessing combined effects of salbutamol and ipratropium bromide in chronic asthma.

We investigated whether salbutamol (S) and ipratropium bromide (IB) exerted a true additive bronchodilator effect in asthma. In fifteen selected chronic asthmatics, individual cumulative dose-response curves to S and IB were performed on two separate days (linear regression of bronchodilator response (delta FEV1) between 20 and 80% of maximal response, versus log dose), and the dose of S equipotent to the IB dose giving the maximal bronchodilator effect (IBopt) was calculated by interpolation of each S curve. On two other days, each patient received IBopt or the equipotent S dose followed by an additional 400 micrograms S. On day 1 or 2, FEV1 reached 220 +/- 410 ml and 2410 +/- 380 ml (p less than 0.05) after the maximal dose of IB and S respectively. On day 3 or 4 after pretreatment by IB or S an additional 400 micrograms S gave a further increase, which was similar in both series (315 and 320 ml, respectively). FEV1 after combination treatment reached 238 +/- 350 ml and was not significantly different from the maximal effect of S (2440 +/- 290 ml). We conclude that S and IB exert a true pharmacological additive effect, since the combination effect is as great as the maximal effect of the most potent drug (S) and greater than the maximal effect of IB, and that the same additional dose of S gives the same increase after equipotent doses of S and IB.

Adult↗
PubMed1987

Effect of cimetidine on the pharmacokinetics of the new beta-blocker betaxolol.

The effect of cimetidine on the new beta-blocker betaxolol (Kerlone) was investigated in 7 healthy volunteers. Propranolol was used as a reference beta-blocking drug. In the control study, a single oral dose of propranolol (80 mg) was given (D0) followed by 5 daily doses of cimetidine (1 g) (D1-D6) and a second oral dose of propranolol (D7). The study was repeated with 20 mg of betaxolol replacing the propranolol dose. The oral clearance of propranolol was significantly decreased (21%). No significant effect of cimetidine on the kinetics of betaxolol was observed.

Adrenergic beta-Antagonists↗
PubMed1987

[Better acceptance of measures for induction of anesthesia after rectal premedication with midazolam in children. Comparison of results of an open and placebo-controlled study].

The rectal administration of midazolam for premedication of children before induction of anesthesia by mask was investigated in two clinical studies. In 62 children aged between 2 and 10 years, midazolam was given by open design at various dosages (0.15 mg.kg-1, 0.25 mg.kg-1, 0.30 mg.kg-1, 0.35 mg.kg-1, 0.40 mg.kg-1) to evaluate the most effective dose for optimal acceptance of the mask and gas mixture. An additional 40 children between 3 and 9 years received 0.2 mg midazolam.kg-1 body weight or placebo in a double-blind design to estimate the lower limit of efficacy of midazolam. All children were classified as ASA I and had to undergo a surgical procedure. Within the two studies the children were not different with respect to their general data, age, weight, and sex. In both studies more boys than girls were included. Parameters of efficacy were the degree of sedation before and at 10, 20, and 30 min after midazolam as well as acceptance of the mask and the gas mixture at induction of anesthesia. In all groups, including placebo, a sedative and tranquilizing effect of the premedication was found. The rectal administration of 0.35-0.4 mg midazolam.kg-1 is most suitable for the preoperative medication of children between 2 and 10 years. Due to the degree of sedation and the relief of anxiety toward the surroundings and the operation, the induction of anesthesia is optimally accepted by the child. In contrast, the effect of a dose around 0.2 mg midazolam.kg-1 body weight is not much different from that of placebo and is not sufficient for effective premedication.

Administration, Rectal↗
PubMed1984

[Premedication using intrarectal midazolam. Study of effective dosage in pediatric anesthesia].

The object of this study was to determine the optimal dose of midazolam given per rectum which would produce sedation adequate for inducing inhalational anaesthesia in paediatric practice. Five doses were studied: 0.15, 0.25, 0.30, 0.35 and 0.40 mg X kg-1. The criteria used to appreciate the effectiveness of the sedation at 30 min were the change in the child's behaviour, with a scale of 6 levels, and the acceptance of the mask and anaesthetic vapours. There was a significant correlation between the dose administered and the degree of sedation, as well as between the dose administered and the lack of reaction to the mask. Significantly better results were found with the higher doses of 0.35 and 0.40 mg X kg-1, when compared with the children who had received 0.15 and 0.25 mg X kg-1. Only in the groups who received 0.35 and 0.40 mg X kg-1 were the degrees of sedation and acceptance of induction considered as adequate. The dose of 0.35 mg X kg-1 seemed to be the best dose for adequately premedicating a child.

Age Factors↗
PubMed1983

[Monotherapy with carbamazepine in childhood epilepsies].

68 epileptic children were treated with carbamazepine (CBZ) monotherapy for a mean period of 10 months. The seizures disappeared in 43% and decreased in another 26.5% of cases. The treatment was particularly efficient in partial benign epilepsies (disappearance: 64.7%, reduction: 29.4%) and in partial unclassifiable epilepsies (disappearance: 50%, reduction: 25%). It is sometimes useful to achieve blood levels over 4 micrograms/ml; but over 8 micrograms/ml the frequency of side-effects becomes greater than improvement of fit frequency. The dose-concentration relation is well correlated to age, so that blood level measurements do not need to be systematically performed. In order to obtain mean blood levels of 7 micrograms/ml 3 to 4 hours after morning intake, mean daily dose should range from: 20 mg/kg/24 h before 5 years to 10 mg/kg/24 h after 10 years.

Adolescent↗
PubMed1982

Pharmacokinetics of tiapride and absolute bioavailability of three extravascular forms.

The pharmacokinetic properties of a single 200-mg dose of tiapride were studied in eight healthy volunteers (four males and four females). The drug was administered by i. v., i. m., and p. o. routes (solution and tablets). Plasma and urine concentrations were determined by a high-performance liquid chromatography. The results were compatible with a linear two-compartment model. The half-life in the disposition phase ranged from 2.19 h to 4.55 h (mean 3.23 h). Peak plasma concentrations were always reached within 2 h. The percentage of absorption of the i. m. and the two p. o. formulations varied from 49.3 to 98.9%. The renal clearance varied from 11.8 to 24.9 l/h. The drug was mainly eliminated in unmetabolized form in the urine (75.6%).

Absorption↗
PubMed1980

Pharmacokinetics of buflomedil after intravenous and oral administration.

Pharmacokinetics studies were conducted in 4 patients who received buflomedil 100 mg intravenously and in 3 volunteers who received buflomedil 450 mg per os. Buflomedil concentrations were determined by a gas liquid chromatography method. Buflomedil levels declined multiphasically with a mean clearance after intravenous administration of -0,034 (1 h-1 kg-1). The decline appeared to be monophasic after oral administration. In both cases the overall half-life is short, mean 2.07 hrs (range, 1,47-2,6 hrs).

Administration, Oral↗