Administration of transgalacto-oligosaccharides increases fecal bifidobacteria and modifies colonic fermentation metabolism in healthy humans.

Transgalacto-oligosaccharides are a mixture of oligosaccharides consisting of glucose and galactose; they are not digested in the human small intestine. In vitro, they specifically stimulate the growth of bifidobacteria. The aim of the present work was to assess tolerance of transgalacto-oligosaccharides and the effects of their prolonged administration on bifidobacteria and fermentative activity of colonic flora. Eight healthy subjects were given 10 g of transgalacto-oligosaccharides per day for 21 d in two daily doses. A breath test and stool sample collection were carried out on d 1, 7, 14 and 21 of transgalacto-oligosaccharides ingestion. The stools of three subjects were collected and mixed before the study, and then inoculated in vitro into a fermentor to which 10 g transgalacto-oligosaccharides was added daily for 14 d. In the eight volunteers, administration of transgalacto-oligosaccharides led to a significant decrease in breath hydrogen excretion (P < 0.01) and a significant increase in fecal concentrations of bifidobacteria from (means +/- SEM) 8.6 +/- 0.6 to 9.7 +/- 0.5, 9.7 +/- 0.6 and 9.5 +/- 0.6 log colony-forming units (CFU)/g on d 1, 7, 14 and 21, respectively (P < 0.05). Fecal concentrations of enterobacteria, as well as stool weight, fecal water and pH did not change during the study. In vitro, transgalacto-oligosaccharides fermentation became more efficient and faster with time. In addition, metabolic alterations such as a rise in acetate proportion and lactate formation after 7 d of fermentation were observed, indicating the transformation of the inoculated fecal flora into an acid-resistant lactic flora. Prolonged administration of transgalacto-oligosaccharides, at a dose which does not induce digestive symptoms, increases the number of bifidobacteria and alters the fermentative activity of colonic flora in humans.

Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers.

OBJECTIVE: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19-34 years, followed for 8 h after each drug administration. METHODS: For i.v. administration the subjects received 4 micrograms dDAVP. For intestinal administration 500 micrograms dDAVP was administered directly, in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml.min-1 for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h. RESULTS: The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml.min.kg-1. The mean bioavailability after duodenal administration of dDAVP+ aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor.

Absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in man.

The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i.v. administration the subjects received 4 micrograms dDAVP. For intestinal administration 400 micrograms dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i.v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml.min-1.kg-1, amount excreted in urine 2.0 micrograms and renal clearance was 0.8 ml.min-1.kg-1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02-0.35%). f was 0.24% after duodenal application (range 0.04-0.62%), 0.19% after jejunal (range 0.01-0.41%), 0.03% after distal ileal (range 0.01-0.08%), 0.04% after proximal colonic (range 0.01-0.12%) and 0.04% after rectal (0.01-0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.