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PubMed1990

The effect of poorly absorbed solute on intestinal absorption.

To determine the effects of poorly absorbed solute on intestinal absorption, the urinary recovery of ingested lactulose, L-rhamnose, D-xylose, and 3-O-methyl-D-glucose was measured after simultaneous ingestion of various 'loads' of mannitol given in iso-osmolar solution. Mannitol reduced intestinal uptake of the poorly absorbed test sugars, lactulose and L-rhamnose; uptake of D-xylose and 3-O-methyl-D-glucose, which are absorbed by carrier-mediated transport largely from the jejunum, was less affected. The dose-response effect of mannitol on the absorption of L-rhamnose was approximately exponential; doses of 5, 10, and 20 g mannitol reduced the average urinary excretion of L-rhamnose by 34.7%, 51.7%, and 61.2%, respectively. In this respect, an osmotically equivalent load of lactulose, ingested as 'solute', was approximately twice as effective as mannitol in reducing L-rhamnose absorption, probably because lactulose is more poorly absorbed than mannitol (less than 1.0% versus 32-41%). Ingestion of other poorly absorbed solutes such as raffinose, sorbitol, xylitol, magnesium sulphate, and sodium sulphate also significantly depressed the absorption of L-rhamnose; in contrast, more efficiently absorbed solutes, such as sodium chloride, glucose, glycerol, and urea had little effect.

3-O-Methylglucose↗
PubMed1989

Intestinal absorption of peptide enteral formulas in hypoproteinemic (volume expanded) rats: a paired analysis.

Previous studies have confirmed the improved tolerance of a peptide enteral compared to standard enteral alimentation in hypoalbuminemic, critically ill patients. Animal studies, including hypoproteinemic, volume-expanded rats, demonstrated that the protein hydrolysate of a peptide enteral formula was responsible for the enhanced absorption. The purpose of this study was to determine whether the composition of small MW peptides (protein hydrolysate) in two commercially available peptide enteral formulas would affect the rate of intestinal absorption and albumin clearance in intact jejunal loops before and during hypoproteinemia induced by iv infusion of Tyrode's solution in Sprague-Dawley rats. Net transmucosal water movement was calculated using a volume recovery method; albumin clearance was calculated using iv radiolabeled albumin. We studied three groups of animals during luminal perfusion with either Tyrode's solution, diet A containing 21% peptides, or diet B containing 56% peptides. When compared to luminal perfusion with Tyrode's solution (control animals), both diets significantly enhanced net transmucosal water absorption before volume expansion (p less than .05). With the induction of hypoproteinemia, diet B continued to stimulate water absorption when compared to control animals (p less than .01). Luminal perfusion with diet A failed to attenuate net water secretion induced by hypoproteinemia. Capillary and mucosal albumin clearance was similar for all groups studied. These findings suggest the percentage of small MW peptides may affect the rate of intestinal absorption in patients with acute kwashiorkor-like hypoalbuminemia.

Animals↗
PubMed1994

Differentiated intestinal epithelial cell lines as in vitro models for predicting the intestinal absorption of drugs.

The oral absorption of a compound is a critical factor for the future of the compound as a drug. This absorption is mainly controlled by the passage across the intestinal epithelium. Thus, the prediction of the intestinal absorption by means of an in vitro model may represent a powerful tool for the early selection of molecules during the process of drug development. In the present study, the differentiated human intestinal epithelial cell line HT29-18-C1, was grown on permeable filters in dual chambers. These cells formed tight monolayers that were used to measure in vitro the transepithelial permeability coefficient (Pc) of various molecules. The results were compared with in vivo data of oral absorption. A threshold value of in vitro permeability of 2 x 10(-6) cm/s was found. Molecules having a permeability coefficient higher than this value were absorbed orally more than 80%, while drugs with Pc values lower than 2 x 10(-6) cm/s were poorly absorbed. By mathematical simulation, it was found that this Pc value, when extrapolated to the surface area and volume of the small intestine, corresponds to an absorption of 80% for a compound with a transit time through the small intestine of 5 h. This demonstrates the predictive utility of the threshold value of the permeability coefficient derived from the in vitro model of intestinal epithelium.

Cell Line↗
PubMed1988

Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid.

Intestinal folic acid transport is a saturable process with a pH optimum of 5.5 to 6.0. Because of the possible effects of antacids and acid-lowering drugs on the pH of the proximal small intestine, the influence of these drugs on folic acid absorption was studied by using tritium-labeled pteroylmonoglutamic acid (PGA) in 30 subjects (21 women, nine men) of 56 to 89 years of age. Both cimetidine and an antacid containing aluminum and magnesium hydroxide reduced folate absorption from a liquid formula meal (p less than 0.01, p less than 0.001, respectively). Although ranitidine also caused a fall in folic acid absorption from the liquid meal, the change was not statistically significantly different from when PGA was given with the meal alone. Both histamine receptor antagonists tended to maintain a high intraluminal pH in the proximal small intestine after meals, which in part could explain the inhibition of folate absorption. However, neither drug was found to chemically interact with folic acid, and neither drug inhibited the dihydrofolate reductase. The antacid was found to precipitate folic acid at a pH of greater than 4.0, thus removing it from the aqueous phase. This appears to be the explanation for the lowered folate absorption in the presence of antacid. Although the effects of these drugs on reducing folic acid absorption were relatively small, such reductions could become clinically significant in chronic antacid or H2 receptor antagonist use or intensive antacid or H2 receptor antagonist use by individuals eating diets that are marginal in folate content.

Aged↗
PubMed1987

Effect of triglyceride on small intestinal absorption of cefoxitin in rats.

Coadministration of trilaurin or monolaurin with sodium cefoxitin increased its absorption from the small intestine of the rat. Its absorption from the rectum was effected to a lesser extent except when lipase was present. Lipase, a natural constituent of the small intestine fluid, may therefore be essential for the adjuvant action of trilaurin on cefoxitin absorption across the intestinal membrane. Among the triglycerides used, trilaurin and tricaprin were the most effective enhancers of cefoxitin absorption. Both the rate of degradation of triglyceride to its fatty acid component and subsequently the rate of fatty acid absorption were factors influencing the enhancing action. Maintenance of fatty acid concentration at the small intestinal absorption site was shown to be necessary to obtain a cefoxitin bioavailability of up to 70%.

Animals↗
PubMed1987

The increase in zincaemia provoked by starvation does not influence the intestinal absorption of zinc.

Serum zinc, measured in obese patients undergoing two weeks of therapeutic starvation (0 kcal, water ad libitum) increased significantly during the starvation period (+48% at day 10) and returned to prestarvation values after refeeding with a 500 kcal diet. Intestinal absorption of zinc was investigated by an oral zinc tolerance test (with 75 mg of zinc acetate) on the second and the tenth day of starvation. No significant differences were observed between the first and the second test. In our experimental conditions 10 days of starvation failed to induce a loss of zinc exceeding 0.75% of the total body stores. It is concluded that the concentration of zinc in blood per se does not regulate intestinal absorption in the absence of a significant change in zinc requirements.

Adolescent↗
PubMed1985

In vitro inhibition of rat small intestinal absorption by lipophilic organic cations.

Cationic, lipid-soluble organic compounds may interfere with cation-mediated membrane transport processes. Thus, small intestinal absorption may be influenced by lipophilic organic cations. Therefore a series of arylalkylamines was studied in the concentration range from 0.5 to 20 mmol/l for their effect on the transport of various monosaccharides and leucine in the rat small intestine in vitro by means of the tissue accumulation technique. Whereas the monophenyl substituted monoamines (e.g. benzylamine, 2-phenylethylamine, 3-phenylpropylamine) did not show a significant effect on the active transport, the corresponding omega,omega-diphenyl derivatives exhibited a strong inhibition of the active transport of the sugars and the amino acid. These monoamines and drugs of similar structure (e.g. benzoctamine, diphenydramine) exhibited a mixed or non-competitive type of inhibition which correlated quite well with their octanol-water partition coefficients. In contrast, di- or triamines (e.g. harmaline, imipramine, pyrilamine) revealed a rather pure competitive type of inhibition. These findings tentatively suggest a different mode of action on the active transport by lipid-soluble organic amines according to the molecular charge distribution. In addition, membrane vesicles were used to examine the effect of the different amines on the sucrase activity. Regarding the cation-dependent hydrolysis of sucrose, however, no distinct pattern developed.

Animals↗
PubMed1985

Aging-associated increase in intestinal absorption of macromolecules.

The intestinal permeability of aging rats to various molecular weight species of polyethylene glycol 400 (PEG 400) was studied. Animals received a bolus of PEG 400 by oral gavage and urine was collected for 6 h to assess its rate of absorption. Quantitation by gas liquid chromatography revealed that total urinary excretion of PEG 400 increased with aging. 34-week-old rats excreted 34.3% of the administrated dose while 43.6% was excreted in the urine by rats 133 weeks of age. This effect was more pronounced with the higher molecular weight PEG since excretion of the lower molecular weight PEG 282 decreased by 10.5% while PEG 634 excretion increased by 11.4% with aging. The increased permeability of the intestinal tract to higher molecular weight species of PEG may indicate that the intestinal protective barrier to the absorption of potentially harmful environmental substances may be less efficient in aging animals. If similar findings are found in aging humans, they may indicate increased potential for absorption of large antigenic or carcinogenic compounds from the intestinal lumen.

Aging↗
PubMedDate not supplied

Prediction of human intestinal absorption of drug compounds from molecular structure.

The absorption of a drug compound through the human intestinal cell lining is an important property for potential drug candidates. Measuring this property, however, can be costly and time-consuming. The use of quantitative structure-property relationships (QSPRs) to estimate percent human intestinal absorption (%HIA) is an attractive alternative to experimental measurements. A data set of 86 drug and drug-like compounds with measured values of %HIA taken from the literature was used to develop and test a QSPR mode. The compounds were encoded with calculated molecular structure descriptors. A nonlinear computational neural network model was developed by using the genetic algorithm with a neural network fitness evaluator. The calculated %HIA (cHIA) model performs wells, with root-mean-square (rms) errors of 9.4%HIA units for the training set, 19.7%HIA units for the cross-validation (CV) set, and 16.0%HIA units for the external prediction set.

Humans↗
PubMed2005

Effect of red wine on the intestinal absorption of thiamine and folate in the rat: comparison with the effect of ethanol alone.

BACKGROUND: This work aimed to investigate, in the rat, the acute in vitro effect of red wine and the effect of chronic red wine ingestion on the intestinal absorption of thiamine and folate and to compare them with the effects of ethanol alone. METHODS: The effects of red wine and of an ethanol solution (same ethanol concentration as that in the red wine, i.e., 12% [v/v]) on rat jejunal apparent permeability (Papp) to H-thiamine and H-folate in the mucosal-to-serosal direction were investigated. Red wine and ethanol were tested both chronically (21-day consumption) and acutely in vitro. RESULTS: Acutely, both red wine and ethanol 12% (v/v) (both diluted 1:5) reduced (to 65 and 60% of control, respectively) the mucosal-to-serosal Papp to H-thiamine across rat jejunum. Chronic (21-day) ethanol (12% [v/v]) consumption also decreased the Papp to H-thiamine (to 33% of control), but red wine consumption for the same period did not change it. Mucosal-to-serosal Papp to H-folate across rat jejunum was not changed by chronic ingestion of red wine or ethanol. Similarly, it was not affected by acute exposition of the tissue to red wine or ethanol. Acute ethanol (0.05% [v/v]) did not affect the Papp to H-thiamine or H-folate in jejunal tissues obtained from control and red wine-treated rats, but it significantly increased the Papp to both H-thiamine and H-folate (to 183 and 197% of control, respectively) in tissues from chronically ethanol-treated rats. CONCLUSIONS: Acute and chronic red wine or ethanol had no effect on the intestinal absorption of folate. However, ethanol, both acutely and chronically, decreased the jejunal absorption of thiamine, and red wine reduced the jejunal absorption of thiamine, but only when tested acutely. These findings show that it is not correct to extrapolate from results obtained with ethanol alone on intestinal permeability to the effect of alcoholic beverage consumption.

Animals↗
PubMed1989

[Disorders of intestinal absorption in patients treated with cytostatic chemotherapy].

We have investigated the acute and chronic side effects of cancer chemotherapy on the intestinal absorption of adult patients with neoplastic diseases. D-xylose absorption was reduced by 35% in 34 of 50 patients within 48 hours after one course (p less than 0.001), while the vitamin B12 absorption was diminished by 41% in 27 of 38 patients (p less than 0.001). The serum digoxin level fell in 7 of 8 patients by 43% at the first day (p less than 0.01) and normalized after one week. Electron microscopy of the jejunal biopsy specimens revealed damages of the microvilli and defects in the glycocalix. Chronic effects, which were measured after several courses and a pause of four weeks, showed a diminished D-xylose absorption of 36% in 16 of 19 cases (p less than 0.01). Vitamin B12 absorption was reduced by 37% in 11 of 13 patients (p less than 0.01). Microscopical investigations of the jejunum revealed a shortening of the villi and a destruction of microvilli. Acute and chronic malabsorption after cancer chemotherapy should be considered in patients, who are treated with enteral medication and nutrition.

Adult↗
PubMed1980

Improving intestinal absorption of water-insoluble compounds: a membrane metabolism strategy.

A strategy for improving the intestinal absorption of water-insoluble drugs was developed and tested. The strategy is based on making a soluble derivative of an insoluble compound which, in turn, is a substrate for enzymes in the surface coat of the brush border region of the microvillous membrane. Consequently, just prior to reaching the membrane, the physical properties of the diffusing species are changed from polar to nonpolar. The experimental test used two drug-drug derivative pairs, estrone-lysine estrone ester and p-nitroaniline-lysine p-nitroanilide. Wall permeabilities were determined using an external perfusion technique in the rat intestine and a laminar flow convective diffusion model for transport in the lumen. Analysis of the permeability results indicates that the derivatives have higher wall permeabilities than the parent compounds and that the microvillous surface coat may be a significant contributor to the intestinal wall resistance. Comparison of the absorption rates for estrone and the lysine estrone ester indicates that the absorption rate of the derivatives could be up to five orders of magnitude greater than that for the parent compound.

Aniline Compounds↗
PubMed1998

Relationships between gastric emptying and intestinal absorption of nutrients and energy in mini pigs.

Little is known about the relationship between gastric emptying of nutrients regulated by feedback mechanisms and the absorptive capacity of the gut. Therefore, we wanted to elucidate these interrelationships. A 150-cm jejunal segment was perfused (1-8 kcal/min) with three different nutrient solutions (either 60% of energy as carbohydrate, or 60% as protein, or 33.3% of each nutrient). In separate experiments, gastric emptying was measured after administration of three different meals with the same nutrient composition as the perfusion solutions. The jejunal absorption of carbohydrate, protein, fat, and energy demonstrated saturation kinetics. The kinetics differed among the three nutrients; carbohydrates were absorbed at higher rates than fat and protein. Interactions among the nutrients altered the kinetics providing a constant absorption of energy. After meals, the stomach emptied equal amounts of energy despite large variations in meal composition. The available intestinal absorptive capacity for protein was utilized by 96%, whereas that for carbohydrate, fat and energy were utilized only by 46-62%. Besides reserves in the absorptive capacity, the intestine provided reserves in total length available for absorption. The results indicate a close relationship between the energy-dependent absorption of nutrients and the energy-dependent feedback inhibition of gastric emptying.

Animals↗
PubMed1985

Intestinal absorption of salicylamide and effect of atropine on it.

The effect of atropine (ATR), a parasynpatholytic agent, on the intestinal absorption of salicylamide (SAM) was studied using the absorption kinetic model proposed by Winne et al. The disappearance of SAM from perfusate and the appearance in intestinal blood were determined using perfused intestinal loop of the rat in vivo. The results showed that the absorption of SAM was simulated by the four compartment model consisting of luminal, interstitial, blood and serosal compartments. The model was assumed to have three rate determining factors, namely mucosal membrane permeability, clearance by blood flow and serosal membrane permeability. ATR decreased the absorption of SAM by decreasing the clearance factor relating to intestinal blood flow and increased the fraction of the transported amount of SAM from interstitial space to serosal compartment.

Animals↗
PubMed2001

Use of an orally administered combined sugar solution to evaluate intestinal absorption and permeability in cats.

OBJECTIVE: To evaluate intestinal permeability and absorption in healthy cats in association with diet and normal intestinal microflora. ANIMALS: 6 healthy domestic shorthair cats. PROCEDURE: A sugar solution containing D-xylose, 30-methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA was administered intragastrically to healthy cats, and urinary excretion of ingested sugars was determined 5 hours after administration. After the same cats had received metronidazole for 1 month, the study was repeated. A final study was performed while cats were maintained on a new diet differing in composition and processing. RESULTS: Lactulose-to-rhamnose ratios, reflecting intestinal permeability, were higher in cats, compared with values for humans or dogs, and values obtained before and after metronidazole administration (mean +/- SEM; before, 0.40 +/- 0.08; after, 0.45 +/- 0.09) were not significantly different. Intestinal absorption also was unaltered after antibiotic administration, and the xylose-to-glucose ratio was 0.70 +/- 0.03 before and 0.71 +/- 0.06 after metronidazole administration. Sugar recovery did not differ significantly while cats were maintained on canned or dry food. CONCLUSIONS AND CLINICAL RELEVANCE: Reference ranges were established for the percentage urinary recovery of orally administered D-xylose, 3-0-methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA obtained after 5 hours in healthy cats. The intestines of cats appear to be more permeable than those of other species, although the normal bacterial microflora does not appear to influence the integrity or function of the feline intestine, because values obtained for the measured variables before or after antibiotic administration were not significantly different. In addition, differences were not detected when the diet was completely altered.

Administration, Oral↗
PubMed1985

Intestinal absorption of ursodeoxycholic, glycoursodeoxycholic and tauroursodeoxycholic acids in rats.

We examined the intestinal absorption of ursodeoxycholic acid (UDC), glycoursodeoxycholic acid (GUDC) and tauroursodeoxycholic acid (TUDC) using an everted gut sac technique. UDC was absorbed throughout rat small intestine almost to the same extent. Absorption of both GUDC and TUDC, however, varied between jejunum and ileum. Absorption of these conjugated bile acids in the jejunal segments was less than that of UDC. While, absorption of GUDC and TUDC in the terminal ileum was more efficient than UDC. Although 2,4-dinitrophenol had no effect on the jejunal uptake, ileal uptake of these three bile acids was inhibited by 2,4-dinitrophenol.

Animals↗