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Biomedical subjects

J Duchier

Publications and source records attributed to J Duchier.

At least 19 recordsLinked to original sources
PubMed2003

[Ethical and legal aspects of biological sample banks: synthesis, practical questions and proposals].

The overview of the numerous ethical questions and complex legal framework regarding biological sample collections leads to present in this synthesis 1) tables of the principal ethical recommendations and French or supranational reglementary texts in this domain, with their internet access; 2) to detail the procedures to follow in some practical situations; 3) to underline the still open questions and current debates, as the ethical and legal framework of human biobanks is in deep evolution.

Bioethical Issues↗
PubMed1993

Pharmacokinetics of lansoprazole in patients with renal or liver disease of varying severity.

The pharmacokinetics of lansoprazole (L) after a single oral dose of 30 mg was determined in 18 healthy volunteers, 17 renal failure patients and 24 hepatic failure patients; 8 hepatitis and 16 with compensated (CC) or uncompensated (UCC) cirrhosis. In renal failure, the absorption of L was unchanged, its half-life being similar to that in healthy subjects; a small change seen in mild renal failure patients (creatinine clearance between 40 and 60 ml/min) was attributed to the age of the patients. Urinary elimination, essentially as metabolites of lansoprazole, was decreased, in relation to the degree of renal impairment. In hepatitis patients, the AUC and t1/2 of L were doubled, without any change in Cmax. In cirrhotics tmax was prolonged, the AUC was increased (P < 0.001) and there was prolongation of t1/2 (6.1 h in CC and 7.2 h in UCC compared to 1.4 h in healthy subjects). These changes resulted from a decrease in the clearance of L. There was also an increase in its sulphone metabolite (Cmax, Rm) and a decrease in the hydroxylated metabolite (Cmax, Rm) in relation to the degree of liver disease, and reflecting a decrease in hydroxylation and biliary elimination. Thus, renal failure had no effect on the pharmacokinetics of L, but severe hepatic failure caused marked changes. A repeated dosing study would be necessary to evaluate the repercussions of the possible accumulation in cirrhotic patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Pharmacokinetics of fluvoxamine maleate in patients with liver cirrhosis after single-dose oral administration.

The pharmacokinetics of fluvoxamine maleate were investigated in 13 patients with biopsy-proven liver cirrhosis. They received a single oral 100mg dose as an enteric-coated tablet, and plasma samples were collected up to 168h after administration. Geometric mean values for peak plasma concentrations and area under the plasma concentration-time curves (AUC) were 39 micrograms/L and 1338 micrograms.h/L, respectively. Mean (+/- SD) elimination half-life (t1/2) was 25 +/- 11h, and increased with higher plasma bilirubin levels, although no relationship between bilirubin and AUC was observed. AUC was about 50% higher in patients than in healthy volunteers from another similar study. This was mainly because of a longer t1/2. Although there is a great overlap between AUC values of fluvoxamine in patients and healthy volunteers, it is nevertheless concluded that in patients with signs of active liver disease, e.g. raised bilirubin, it is wise to lower the initial daily dose and to carefully monitor the patient during subsequent upward dose adjustments.

Administration, Oral↗
PubMed1992

Dose ranging study of lansoprazole, a new proton pump inhibitor, in patients with high gastric acid secretion.

The effects of single doses and of 7 days of lansoprazole 10, 20 and 30 mg PO versus placebo on gastric acid secretion have been evaluated in 8 patients with high gastric acid secretion. The double blind crossover period was followed by a simple blind 7 days on placebo to detect any rebound phenomenon. After the first dose lansoprazole did not modify basal acid output (BAO) but it significantly and dose dependently inhibited peak acid output (PAO) and increased the time during which nocturnal intragastric pH was greater than 3. After 7 days of treatment the same significant, dose-dependent suppression of gastric acid was found, but BAO was also blocked. One week after cessation of lansoprazole administration no rebound increase in gastric acid-secretion was observed. The plasma gastrin concentration remained unchanged throughout the study.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Hemodynamic effects of carvedilol after acute oral administration in hypertensive and normal subjects.

Forearm hemodynamics using pulsed Doppler flowmetry were studied in nine healthy volunteers and 12 patients with mild-to-moderate hypertension before and after acute oral administration of the beta-blocking and vasodilating agent carvedilol. Both the 25- and the 50-mg dose produced a significant blood pressure reduction by comparison with placebo in normotensive and hypertensive subjects. Only the 50-mg dose caused a decrease in forearm vascular resistance in hypertensive subjects. The decrease disappeared after wrist occlusion. Although brachial artery diameter did not change, a significant decrease in tangential tension was observed. This study provides evidence that carvedilol produced arteriolar dilation within the forearm of hypertensive subjects in association with a decrease in brachial artery tangential tension.

Administration, Oral↗
PubMed1990

Stereoselective protection of exogenous and endogenous atrial natriuretic factor by enkephalinase inhibitors in mice and humans.

We compared the relative potencies of sinorphan and retorphan, the S- and R-enantiomers of acetorphan a potent inhibitor of enkephalinase (EC 3.4.34.11), to inhibit membrane metalloendopeptidase in vivo and to protect exogenous and endogenous ANF after oral administration. In mice, sinorphan was 2-3 fold as potent as retorphan in inhibiting the specific in vivo binding of [3H]acetorphan to kidney enkephalinase. The same potency ratio was found for the enhancement of trichloroacetic acid-precipitated radioactivity in kidneys of mice that had received 125I-ANF, which is used as a test for the protection of the hormone against inactivation in vivo. In nine healthy human volunteers who had received a low oral dosage of sinorphan or retorphan in a double-blind, placebo-controlled, randomized trial, sinorphan was also 2-3 fold more potent than retorphan in inhibiting plasma enkephalinase activity. These effects were accompanied by a related rise in plasma ANF immunoreactivity, which also reflected the difference in the effectiveness of the two compounds. Sinorphan was also more potent than retorphan in enhancing urinary cyclic GMP excretion and sodium excretion in five of these subjects. These data indicate that, in humans as in rodents, enkephalinase plays a crucial role in the inactivation of ANF, its partial inhibition in vivo being accompanied by a significant protection of the exogenous or endogenous hormone as well as by typical ANF-like responses. Thus orally administered sinorphan appears to be a promising compound for therapeutic use in cardiovascular and renal diseases in which ANF has been postulated to exert beneficial effects.

Administration, Oral↗
PubMed1990

Peripheral haemodynamic effects of smoking in habitual smokers. A methodological study.

The effect of smoking on forearm haemodynamics was studied in four groups of healthy subjects, who had all smoked cigarettes (10-15 cigarettes/day) on average for 10 years. Changes in heart rate, blood pressure, forearm blood flow, forearm vascular resistance and pulse wave velocity were determined before and every 15 min for 75 min after smoking two cigarettes within 10 min. The inhaled nicotine was about 2.2 mg. There was no significant difference between the four groups in any haemodynamic variable before or after smoking, which indicated adequate reproducibility of the parameters studied and so made it possible to pool the results from all 30 subjects. Smoking significantly increased blood pressure, heart rate and pulse wave velocity and decreased forearm blood flow. Forearm vascular resistance remained unchanged. The rises in systolic blood pressure and pulse wave velocity were transient and both peaked (7% and 28%, respectively) 15 min after smoking. In contrast, heart rate and diastolic blood pressure remained significantly elevated and forearm blood flow was significantly decreased throughout the 75 min follow-up. The maximal changes were: heart rate +34%, diastolic blood pressure +17%, and forearm blood flow -24%. It is concluded that smoking produces statistically significant changes in forearm haemodynamics affecting both small and large arteries. The reproducibility of the study design means that it can be used to evaluate substances which may antagonize the haemodynamic effects of tobacco smoking.

Adult↗
PubMed1990

Plasma and urine aluminium concentrations in healthy subjects after administration of sucralfate.

1. Sucralfate (basic sucrose aluminium sulphate), a topical intestinal agent, was administered in suspension or granule form to 25 healthy subjects at a total dose of 4 g day-1 for 21 days. Aluminium in plasma and 24 h urine samples was assayed before, during and after administration of sucralfate by inductively coupled plasma optical emission spectrometry. 2. Sucralfate produced significant increases in plasma and urine aluminium concentrations. On average, plasma aluminium increased from about 2 micrograms 1-1 to more than 5 micrograms 1-1 and 24 h urine aluminium increased from less than 5 micrograms to more than 30 micrograms. Both plasma and urine aluminium concentrations decreased rapidly after sucralfate was stopped. However, urinary aluminium concentrations remained higher than normal 5 and 10 days after discontinuation of sucralfate administration. Moreover subjects receiving sucralfate granules had significantly higher average urinary excretion of aluminium than subjects receiving the suspension. 3. The small but significant increase in plasma and urine aluminium following sucralfate administration in therapeutic doses may reflect intestinal absorption of aluminium. Although such absorption would appear to be moderate in healthy subjects, it is suggested that aluminium-based treatments should be used only intermittently, especially in patients with renal disorders.

Adult↗
PubMed1990

[Current practice of drug trials in healthy volunteers].

It is impossible to extrapolate for men the animal's data. Pre-therapeutical studies are a necessity to state precisely in man ADME for a new drug and to confirm pharmacological properties seen in animals. Very often, the only healthy volunteers are useful for Phase 1 studies: The selection of volunteers keeps physical and metabolic status, and psychological motivation. True but restricted information is necessary for "free and informed consent". Rights and duties must be clearly defined in written convention. Financial advantages are in agreement of trouble but not of hazard in the study. The safety is the main point in human studies. That means a safe methodology and a protocol approved by independent ethical committee. The monitoring of these studies must be precisely conducted with many clinical and laboratory examinations. Healthy volunteers studies are required by French Ministry of Health, rejected by medical law, condemned by civil law but covered by legal insurances. In French mind is illicit that is not specifically permitted by law. We need special legislation as we refuse medical and ethical responsibility.

Adult↗
PubMed1989

Calcium blocker lacidipine and carotid arteriolar vasodilation in healthy volunteers.

Systemic and carotid hemodynamics were studied in 10 healthy male volunteers before and after short-term administration of a 4 mg dose of the calcium entry-blocker lacidipine in a placebo-controlled, double-blind, crossover study. Hemodynamic parameters of the right common carotid artery were measured before and at 1 1/2 and 3 hours after dose administration by means of pulsed Doppler flowmetry. In addition, systemic hemodynamic parameters were calculated from cardiac impedance measurements at the same time. In comparison with placebo, lacidipine produced a significant decrease in blood pressure, together with systemic and carotid arteriolar dilatation. Heart rate increased sharply, whereas carotid arterial diameter and tangential tension did not change. The study provided evidence that the calcium entry-blocker lacidipine produces systemic and carotid arteriolar vasodilation and that the heart rate baroreflex response after administration of calcium inhibitor is not associated with a significant modification of the geometry of carotid arterial wall.

Administration, Oral↗
PubMed1989

Protection of atrial natriuretic factor against degradation: diuretic and natriuretic responses after in vivo inhibition of enkephalinase (EC 3.4.24.11) by acetorphan.

Atrial natriuretic factor (ANF) might be beneficial in several cardiovascular disorders, but its poor oral absorption and rapid inactivation in vivo have so far prevented its use in therapeutics. We have assessed the role of enkephalinase (membrane metallo-endopeptidase, EC 3.4.24.11) in the in vivo inactivation of ANF in mice and healthy human volunteers by evaluating the effects of acetorphan, a potent inhibitor. In mice, the degradation of 125I-labeled ANF was markedly delayed, as shown by the levels of the intact peptide in the plasma and the kidney, a major target organ. The effect of acetorphan was due to the inhibition of enkephalinase activity, since it occurred at an ED50 very close to this drug's ID50 for the inhibition of the specific binding of radioactive material to the kidney or lung peptidase that was measured after administration of [3H]acetorphan. The effects of acetorphan were also studied in eight healthy human volunteers by using a randomized double-blind, placebo-controlled design. Oral administration of acetorphan elicited a lasting elevation of plasma ANF-like immunoreactivity, with a time course parallel to that of the inhibition of plasma enkephalinase activity. These effects were accompanied by significant increases in urinary volume and sodium excretion, two well-established renal responses to ANF peptides. These results indicate that enkephalinase plays a critical role in ANF degradation in vivo and that its inhibition enhances the levels of circulating endogenous ANF, which, in turn, results in diuresis and natriuresis. Enkephalinase inhibition may constitute another therapeutic approach to the treatment of cardiovascular diseases, such as congestive heart failure or essential hypertension, on which ANF is postulated to have a beneficial effect.

Animals↗
PubMed1989

Effects of twenty-four hours of bed rest with head-down tilt on cardiopulmonary baroreflex control: preliminary study.

The cardiopulmonary baroreflex response was studied before and after 24 h bed rest with head-down tilt (-5 degrees) in six normal male subjects, through lower body negative pressure (-5, -10, -15 mmHg) and passive leg raising. The reflex response was assessed (using plethysmography) by changes in forearm vascular resistance. During the lower body negative pressure and leg raising, forearm vasoconstriction and vasodilation were similar before and after head-down tilt. The study shows that orthostatic intolerance following head-down tilt is not explained by an abnormality in the response of low pressure baroreceptors.

Adult↗
PubMed1989

Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

1. The kinetics and dynamics of long acting propranolol 80 mg and 160 mg were examined after single oral doses to 12 healthy volunteers. 2. Long acting propranolol 160 mg produced a twofold increase in mean peak blood propranolol concentration and AUC compared with the lower dose. There was no difference in elimination half-life, bioavailability and mean residence time of propranolol between the two doses. 3. Resting pulse rate was decreased by long acting propranolol 160 mg but not by the lower dose. 4. Both preparations blocked exercise induced tachycardia during the entire observation period of 29 h. Percentage inhibition of exercise tachycardia was significant at all time points but long acting propranolol 160 mg exhibited a greater reduction at 24 h and 29 h. 5. Increase in systolic blood pressure during exercise was inhibited by both preparations during the entire observation period with no differences between them. 6. The doubling of the dose administered was reflected in blood concentrations but not in pharmacodynamic parameters. Few pharmacodynamic differences were found between the two doses.

Adult↗
PubMed1989

[Evaluation of the effectiveness of a cicletanine-enalapril combination in hypertensive patients].

In this multicentre controlled single blind trial the effectiveness and safety of cicletanine (100 mg/day) were compared with those of enalapril (20 mg/day) and of the combination of both drugs in the same doses in 72 patients (41 men, 31 women, mean age 64.1 +/- 8.3 years) with permanent moderate essential hypertension without severe cardiovascular complications. In the course of the trial, one patient in each of the three therapeutic groups was excluded either for insufficient effectiveness in monotherapy or for photosensitization under the combined treatment. After two months of treatment, the fall in blood pressure and the number of patients with normalized BP were similar in the groups treated with cicletanine or enalapril alone. In contrast, the cicletanine-enalapril combination produced a significantly greater fall of diastolic arterial pressure than cicletanine alone. In addition, there was a greater reduction of functional symptoms associated with arterial hypertension. Apart from the lone case of photosensitization observed with the combined treatment, only minor side-effects were encountered, including an episode of diarrhoea and a case of extrasystoles with the combination, and a case or nausea with lipothymia under cicletanine alone. There were no significant variations of biochemical values.

Aged↗
PubMed1989

Effect of Ginkgo biloba extract on microsomal enzyme induction.

Twenty-four healthy volunteers were divided in three groups who were randomly assigned different treatments for 13 days: group I received 400 mg/day of a defined Ginkgo biloba extract (GBE), group II 300 mg/day of phenytoin and group III a placebo. The elimination half-life of antipyrine was measured with a high performance liquid chromatographic technique initially and on the last day of the administration of the treatments. The results show that the half-life of antipyrine was not affected by GBE and placebo treatments, whereas it was significantly decreased (p less than 0.05) frm 12.2 to 6.8 h after phenytoin control treatment. This study demonstrates that GBE has no effect on the hepatic microsomal drug oxidation system.

Adult↗