Biomedical subjects

N Vidon

Publications and source records attributed to N Vidon.

At least 19 recordsLinked to original sources

PubMed1992

Absorption of a nutrient solution in chronic alcoholics without nutrient deficiencies and liver cirrhosis.

Duodenal and jejunal absorption of a nutrient solution at two different caloric loads (1.32 and 3.96 kcal/min = 5.6 and 16.8 kJ/min) was compared in chronic alcoholics without malnutrition, liver cirrhosis, obvious small-bowel dysfunction, and exocrine pancreatic insufficiency and in an age-matched control group, by means of the intestinal perfusion technique. In chronic alcoholics duodenal net absorption of water (p < 0.025), sodium (p < 0.02), potassium (p < 0.005), total nitrogen (p < 0.02), carbohydrates (p < 0.05), and lipids (p < 0.05) was lower than in controls when both caloric loads were administered, but jejunal absorption rates were not decreased. Biliopancreatic secretion did not differ between alcoholics and controls. Higher serum protein leakage in alcoholics was indicated by an increased (p < 0.01) duodenal alpha 1-antitrypsin clearance under low caloric load infusion. It is concluded that the absorptive function of the duodenum is impaired in alcoholics, whereas the upper jejunum is not affected.

Adult↗

PubMed1991

Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations.

The effect on steatorrhoea of a pH-sensitive enteric-coated pancreatic preparation (Eurobiol 25,000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25,000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P less than 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno-jejunal flexure were significantly improved (P less than 0.05). Marked inter-individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric-coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric-coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying.

Adult↗

PubMed1991

Human jejunal secretion induced by prostaglandin E1: a dose-response study.

1. Intraluminally infused prostaglandins induce jejunal secretion of water and electrolytes in man, and a receptor-mediated process in the intestinal epithelial cells has been suggested to explain this secretion. In an attempt to obtain data under basal conditions for pharmacological studies, we tested the dose-response effect of PGE1 on jejunal hydroelectrolytic movements in 10 healthy volunteers. 2. Accordingly, a solution with or without PGE1 was infused via a four-lumen tube with a proximal occluding balloon and jejunal water and electrolyte transport were determined. The segment tested was 40 cm long. Seven randomized doses of PGE1 ranging from 0.01 to 1.3 micrograms kg-1 min-1 (2.83 to 364 pmol kg-1 min-1) were infused in an isotonic control saline solution. The secretion induced by PGE1 was evaluated in each subject as the difference between fluxes in response to the control saline solution and to PGE1. 3. Whatever the dose, PGE1 induced secretion of water, Na+, K+ and Cl- which was dose-dependent and saturable, with a mean Km of congruent to 6-8 pmol kg-1 min-1, suggesting that at the pharmacological doses used, enterocytes have a saturable membrane site similar to a single class of receptor for PGE1. 4. These findings may be of great importance if prostaglandins are administered as drugs or used as jejunal secretory agents in vivo when the antisecretory effect of another drug is studied.

Adult↗

PubMed1990

Intestinal absorption of amiodarone in man.

The jejunal absorption rate of amiodarone and the influence of lipids on it were studied in human volunteers using the intestinal perfusion technique. A nutrient solution (Realmentyl, Sopharga Laboratories, France) with 300 mg of the drug was infused for 120 minutes at the ligament of Treitz. The segment tested was 25 cm long. Two caloric loads of the nutrient solution, 3.3 Kcal/min (solution A) and 1.3 Kcal/min (solution B), A containing total lipid and caloric load 2.5 times higher than B, were administered. Minor interindividual differences in amiodarone absorption rate were observed (20.2 to 31.7%) with solution A. Amiodarone absorption correlated with lipid absorption significantly. Since the maximal plasma concentrations of the drug and the area under the curve (AUC/24 hours) did not correlate with the amount of amiodarone absorbed, the wide fluctuations of amiodarone pharmacokinetics must mainly be due to amiodarone tissue distribution and metabolic pathway.

Administration, Oral↗

PubMed1989

Almitrine bismesylate disposition in the human digestive tract.

The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker 14C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected. Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time. The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.

Adult↗

PubMed1989

Inhibitory effect of high caloric load of carbohydrates or lipids on human pancreatic secretions: a jejunal brake.

Effects of jejunal infusion of a saline solution, a protein meal, and a mixed protein and carbohydrate meal on biliopancreatic secretions were compared in six healthy volunteers. Protein infusion stimulated biliopancreatic secretions whereas carbohydrate infusion inhibited these secretions compared with saline infusion. The roles of lipid, carbohydrate, and caloric load on the inhibition of pancreatic secretions by jejunal infusion of nutrients was investigated in six other healthy volunteers. Carbohydrate, lipid, and the mixed meal inhibited pancreatic secretions whereas the carbohydrate solution was the only one that inhibited biliary secretion. These studies indicate that the mechanism of jejunal brake seems mainly related to the jejunal caloric load. In malabsorption or in the short bowel syndrome, a high caloric load or unabsorbed nutrients in the jejunum further inhibits pancreatic secretion, contributing to the loss of nutrients from the intestinal tract.

Adult↗

PubMed1989

Evaluation of the gastric absorption and emptying of drugs under various pH conditions using a simple intubation method: application to diclofenac.

Sodium diclofenac (50 mg) together with [14 C]-PEG as a non-absorbable marker were dissolved in 400 ml of water (A), phosphate buffer pH 7.5 (B) or a homogenized meal (C). Each of these was ingested in random order by six volunteers on 3 consecutive days. Some gastric absorption of the drug was established with C but the plasma drug concentration-time profiles mainly reflected the process of gastric emptying.

Absorption↗

PubMed1989

Effect of jejunal infusion of nutrients on gastrointestinal transit and hormonal response in man.

The effects of jejunal infusion of nutrients on gastric emptying and secretion, intestinal transit and hormone release were studied in human volunteers. Two caloric loads, 1.3 and 3.3 kcal/min, of a nutrient solution consisting of 18 percent protein, 27 percent lipids, and 55 percent carbohydrates were tested. These were first used in random order in 6 subjects to assess the effects on intestinal transit. For the study of gastric emptying, jejunal infusion was started 1 h after intragastric instillation of a 490 kcal, 400 ml, homogenized meal. Intestinal transit time and gastric emptying half-time increased with the rate of nutrient infusion into the jejunum. Postprandial gastric secretion was reduced. The two caloric loads induced significant rises of plasma cholecystokinin and gastric inhibitory polypeptide concentrations. Plasma motilin decreased in relation to the jejunal caloric load. The other peptides were essentially not affected by jejunal nutrient infusion in fasting subjects. We conclude that in man, gastric emptying rate, gastric secretion, and intestinal transit are regulated by the presence of nutrients in the jejunum.

Adult↗

PubMed1988

Metformin in the digestive tract.

After ingestion of metformin, a drug of the biguanide class, there are gastrointestinal effects in the form of nausea and vomiting, and about 30% of the drug is recovered in feces. The purpose of this work was to explain these two phenomena. Two sets of experiments were carried out. Study I evaluated the gastroduodenal (GD) absorption in six healthy volunteers by means of an intubation method, employing a twin-lumen tube introduced into the intestine and another into the stomach. Metformin 1 g was introduced into the stomach with a homogenized meal containing a non-absorbable marker, 14C-PEG 4000; another marker, PEG 4000, was perfused continuously into the duodenum at the ampulla of Vater. Samples of GD contents were collected every 15 min during 4 h. Metformin was poorly absorbed from the stomach, about 10% over a 4-h period. It did not modify the gastric emptying of a meal but induced a duodeno-gastric reflux in five out of six subjects. About 20% of the amount of drug emptied from the stomach were absorbed from the duodenum. The delivery process was the rate-limiting factor for metformin absorption from the duodenum. The AUC/24 h increased as the absorption rate from the duodenum increased. Study 2 investigated in six healthy volunteers, using another intestinal perfusion technique, the jejunal and ileal absorption of metformin. Metformin 400 mg in saline solution was perfused, over a 2-h period, below an inflated balloon, directly into either the jejunum or the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Influence of digestive secretions and food on intestinal absorption of nicardipine.

The role of digestive absorption in the pharmacokinetics of nicardipine has been studied by the perfusion technique. Nicardipine (40 mg) was perfused in six healthy subjects at 5 ml/min for 2 h either in isotonic saline with (Experiment A) or without (B) an occlusive balloon isolating the test segment from digestive secretions, or in a nutrient solution (Experiment C). In Experiments A and B, 100% of nicardipine was absorbed from the jejunal lumen in a 25 cm test segment and in Experiment C it was slightly lower (94%). There was no relationship between the absorption of nicardipine and water movement or bile salt concentration in the jejunum. Nicardipine was already present in the first plasma sample taken after 15 min and the peak level was found at the end of the perfusion. The areas under the curves differed widely between subjects, because of interindividual variation in the first pass effect, but they were similar in Experiments A, B and C. The experimental data showed a good fit to a mode involving a two-phase absorption process. The first phase was associated with intestinal perfusion (zero order process) and the second with passage across the intestinal wall (1st order process). In three further healthy subjects, nicardipine in saline was perfused in the jejunum and then in the ileum on consecutive days. Mean plasma levels over time were similar. The study showed that absorption of nicardipine both from the jejunum and the ileum was complete and was especially rapid. The food-induced change in the kinetics of absorption from the jejunum was too small to affect the pharmacokinetic parameters of nicardipine.

Adult↗

PubMed1988

Effect of different caloric loads in human jejunum on meal-stimulated and nonstimulated biliopancreatic secretion.

The effects on biliopancreatic secretion of two caloric loads (1.3 and 3.3 kcal/min of Realmentyl: proteins 18%, lipids 27%, carbohydrates 55%), infused into the jejuna of 10 healthy men, were compared with those of a control solution. In one set of experiments (six subjects) when biliopancreatic secretion was not stimulated before infusion, the rate 1.3 kcal/min resulted in mild stimulation whereas the rate 3.3 kcal/min brought about an inhibition of biliopancreatic secretion. In another set of experiments (six subjects) when biliopancreatic secretion was stimulated by ingestion of an homogenized meal (400 mL, 490 kcal) 1 h before the start of infusion, both loads resulted in strong inhibition of pancreatic secretions, the effect being more pronounced with the high caloric load.

Adult↗

PubMed1987

Jejunal and ileal absorption of oxprenolol in man: influence of nutrients and digestive secretions on jejunal absorption and systemic availability.

1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxprenolol was absorbed in the jejunum and 48% in the ileum; the differences were significant. 3 The plasma concentration-time profiles were similar for the two perfusions. The AUC and Cmax values of free and conjugated oxprenolol for the jejunal perfusion were significantly lower than those of ileum. They showed large but consistent intersubject variations in the two treatments. 4 Study II investigated, using the same technique, the influence of nutrients and digestive secretions on jejunal absorption and systemic availability of this drug. A saline (in treatments A and B) or a nutrient (in treatment C) solution containing oxprenolol was perfused into the jejunum below a balloon either inflated (A) or deflated (B and C). 5 The disappearance rate of oxprenolol from the jejunum was unaffected by endogenous secretions. The mean amount of drug absorbed along a 30-cm jejunal segment accounted for 52 (A) and 57% (B) of the total amount perfused. The intestinal absorption rate was markedly increased in the presence of nutrients (mean amount absorbed 96% for C). 6 The change in the rate of disappearance from the intestine had no effect on the systemic availability of oxprenolol (mean AUC values 8740, 8250 and 8020 nmol l-1 h for A, B and C, respectively) or its elimination from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Availability↗

PubMed1986

Influence of bile salts and lipids on intestinal absorption of griseofulvin in man.

The influence of bile salts and lipids on the intestinal absorption of griseofulvin has been studied in 11 healthy male volunteers by the intestinal perfusion technique. The drug in a nutrient solution (Realmentyl) was perfused into the second part of duodenum at 5 ml/min. Intestinal samples were taken continuously at 1 ml/min, 20 cm (at the angle of Treitz) and 45 cm distal to the perfusion point. To study the effect of lipids on griseofulvin absorption, the drug was perfused with solutions A and B, of which B contained a total lipid and caloric load three times that of A. The influence of bile salts on griseofulvin absorption was examined by perfusing the drug on Day 1 with bile salts and again on the following day after bile salt depletion. Bile salts and a varying quantity of lipid perfusate had no significant influence on the duodeno-jejunal griseofulvin absorption rate per cm of intestine. Lipids, however, may still play a role in griseofulvin absorption along the entire intestine.

Adult↗

PubMed1986

Gastric clearance of alpha-1-antitrypsin under cimetidine perfusion. New test to detect protein-losing gastropathy?

Gastric losses of plasma are usually measured with radiolabeled macromolecules. This method is expensive and cumbersome. Direct measurement of exudated plasma proteins are ineffective since proteins are denaturated by acidic gastric juice and pepsin. It was recently shown that albumin measurement after immediate neutralization allowed detection of gastric protein losses, but this method is quite complex and time consuming. We studied alpha 1-antitrypsin and 51Cr-labeled protein clearance in gastric juice during normal saline and cimetidine (1.5 mg/kg/hr) infusion in six healthy volunteers and six patients with exudative gastropathy. alpha 1-Antitrypsin was measurable in all samples during cimetidine infusion: alpha 1-AT and 51Cr losses were significantly correlated (P less than 0.001). The upper limit of gastric alpha 1-AT clearance in controls was 0.86 ml/hr (mean + 2 SD). Using this value, there was no overlapping between patients and controls. The upper limit of 51Cr test was 1.87 ml/hr (mean + 2 SD) in controls but gastric clearance of 51Cr was below this value in one patient. This suggests that the measurement of alpha 1-AT gastric clearance during cimetidine perfusion is a good test to detect an exudative gastropathy. This test is inexpensive and lasts only 3 hr.

Adult↗

PubMed1986

[Influence of Saccharomyces boulardii on jejunal secretion in rats induced by cholera toxin].

The effects of a suspension of Saccharomyces boulardii cells on water and sodium secretion induced by cholera toxin was measured in male Wistar rats weighing 220-260 g, using the isolated jejunal loop technique. Concentrations per ml of 3.1 X 10(9), 2.1 X 10(9) and 0.7 X 10(9) viable cells and 3.1 X 10(9) cells killed by irradiation or heating respectively were tested. At this last concentration, the supernatant obtained after centrifugation of the suspension of living cells or of cells killed by irradiation was also tested. Four 10 cm-long loops, the first one beginning at the angle of Treitz, were isolated: the first two loops with and without S. boulardii, the other two (previously incubated with cholera toxin for 3 h) with and without the cells. Each loop contained 1.5 ml of test solution or suspension. S. boulardii living cells had no effect on water and sodium basal intestinal transport but significantly reduced water and sodium secretion induced by cholera toxin within 20 min. Irradiation and heating did not abolish this antisecretory effect while the supernatant obtained after centrifugation of living or irradiated cell suspensions had no inhibitory effect.

Animals↗

PubMed1985

Effect of increased amounts of pectin on a solid-liquid meal digestion in healthy man.

The effect of three concentrations of high-methoxy apple pectin (5, 10, and 15 g), on solid-liquid meal digestion was studied in 12 healthy men by the gastrointestinal intubation technique. The gastric emptying of water and carbohydrates is significantly reduced only after 10 and 15 g pectin. The changes in gastric pH are similar for pectin-free and pectin-containing meals. Cumulative lipase and trypsin outputs are not significantly different with and without pectin. When gastric uronic acid concentration is above 6 g/l, the duodenal absorption of carbohydrates is significantly reduced (p less than 0.001). The mean blood glucose levels with 10 and 15 g pectin are significantly higher than the control values at 180 min (p less than 0.05). Pectin does not modify serum concentrations of secretin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), and somatostatin but serum motilin and gastrin levels are below the control values after high fiber meal.

Adult↗

PubMed1985

Investigation of drug absorption from the gastrointestinal tract of man. II. Metoprolol in the jejunum and ileum.

Absorption of metoprolol in jejunum and ileum was investigated in eight healthy subjects using an intestinal perfusion technique below an occlusive balloon. An isotonic saline solution, with or without metoprolol, was perfused at a flow rate of 10 ml/min, either at the angle of Treitz or in the middle part of the ileum. The absorption in a 30 cm intestinal segment was evaluated at metoprolol concentrations of 20, 40 and 60 mg/l. Metoprolol did not affect gut motility. Metoprolol was similarly absorbed in the jejunum and ileum. The absorption rates appeared to be linearly related to the perfusion rates and to the mean concentration in the segment, indicating a first-order kinetic process. The absorption rate of metoprolol perfused in the jejunum in a saline solution appeared to be lower than that observed after gastric administration of the drug incorporated in a meal. The findings in this and other studies in this series indicate that metoprolol is similarly absorbed throughout the small intestine.

Adult↗

PubMed1985

Investigation of drug absorption from the gastrointestinal tract of man. III. Metoprolol in the colon.

The colonic absorption of metoprolol was indirectly evaluated by measuring drug appearance in plasma following intravenous, jejunal or colonic infusion in six healthy volunteers. Plasma concentrations of alpha-hydroxymetoprolol and urinary excretion of the main metabolites were also measured. Plasma profiles of metoprolol after colonic and jejunal perfusion were similar, and the relative bioavailabilities of the drug from these two regions of the gut were not significantly different. The concentrations of alpha-hydroxymetoprolol, the major metabolite in plasma, were similar after jejunal and colonic perfusion, but higher than those observed after intravenous administration. The percentage of the dose recovered in urine over 24 h as two metabolites was not significantly influenced by the route of administration.

Adult↗