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PubMed1995

Enhanced intestinal absorption of oxytocin peptide analogues in the absence of pancreatic juice in pigs.

PURPOSE: The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. METHODS: In conscious chronically catheterized pigs (6-8 weeks of age) plasma concentration of the peptides, [Mpa, D-Tyr(Ethyl), Thr, Orn]-oxytocin (F314), [Mpa, D-Tyr(Ethyl), Val, D-Arg]-oxytocin (CAT), and [Mpa, D-Tyr(Ethyl), Thr, Orn, desGly, carba]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. RESULTS: All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. CONCLUSIONS: The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.

Animals↗
PubMed2003

Intestinal absorption of disodium monofluorophosphate in the rat as affected by concurrent administration of calcium.

This paper reports that in the rat coadministration of calcium (calcium chloride, CAS 10043-52-4, Ca2+) enhances intestinal absorption and bioavailability of monofluorophosphate (sodium monofluorophosphate, CAS 10163-15-2, MFP). Evidence obtained with two different experimental models is presented indicating that the latter effects are indirect consequences of the inhibitory effect of Ca2+ on alkaline phosphatase. Pharmacokinetic experiments in previous studies showed that fluorine bound to plasma proteins is the variable that determines the bioavailability of MFP. The area under the curve of fluorine bound to plasma proteins in rats receiving MFP + Ca2+ was significantly greater than in controls. In isolated duodenal loops in situ, Ca2+ increased the intestinal rate constant of MFP absorption and decreased the rate constant of MFP hydrolysis. Inhibition of hydrolysis increased the concentration of MFP at the intestinal lumen. This fact, however, is not only the cause of increased MFP absorption. Inhibition of alkaline phosphatase with L-phenylalanine, to the same extent as with Ca2+, increased MFP absorption with respect to controls but to a lower degree than with Ca2+. The rate constant of MFP hydrolysis by purified rat intestinal alkaline phosphatase was significantly inhibited by 50 mmol/l Ca2+ in comparison to control levels. Ca2+ decreased significantly Vmax of the enzyme (p-nitrophenyl phosphate as substrate) and had no effect on Km value. Lineweaver-Burk plots suggested a noncompetitive inhibition mechanism.

Alkaline Phosphatase↗
PubMed1983

Intestinal absorption, excretion, and biotransformation of hyodeoxycholic acid in man.

Five patients fitted with a biliary T-tube after cholecystectomy were given orally a tracer dose of [14C]hyodeoxycholic acid and 500 mg of the same unlabeled acid. Intestinal absorption and biotransformation, liver metabolism, bile secretion, fecal and urinary excretions of this acid or of its metabolites were studied. Hyodeoxycholic acid was well absorbed by the human intestine. It was not subjected to intestinal transformations and, particularly, did not produce a significant amount of lithocholic acid, which does not support the existence of intestinal bacterial 6 alpha-dehydroxylases. The percentage of hyodeoxycholic acid and of its metabolites recovered in bile varied from 11.5 to 31%. Two major metabolites were isolated from bile: glycohyodeoxycholic acid and hyodeoxycholic acid glucuronide. Analysis of urinary bile acids showed that a large proportion (30-84%) of the administered hyodeoxycholic acid was excreted by the kidney as a glucuronide. The large extent of both glucuronidation and urinary excretion of hyodeoxycholic acid is a unique example of bile acid metabolism and excretion in man.

Adult↗
PubMed1996

Baclofen: intestinal absorption mechanism in mice.

1. The duodenal transfer of baclofen from sacs of mouse intestine was determined. 2. A linear relationship between the steady-state transfer rate of total and the initial mucosal baclofen concentration was observed, suggesting that the clearance is the same at different concentrations. 3. There was no significant difference in the amount of total drug removed between control and everted tissues. 4. The data support the idea that the principal transfer mechanism for baclofen is simple diffusion in mouse intestine.

Animals↗