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Does the non-absorbable fat, (sucrose polyester), interfere with the intestinal absorption of vitamin A?

Sucrose polyester (SPE) is a synthetic non-absorbable lipid. The effect of SPE on vitamin A absorption was determined by monitoring the disappearance rate of radio-labeled vitamin A from the jejunal perfusate of the rat. The relative distribution of radio-labeled vitamin A between the micellar phase and the perfusate containing SPE was determined. With SPE concentrations of 5, 10 and 20 g/l, vitamin A was concentrated in the SPE phase over the micellar phase by a factor of 4.4, 9.4, 19.8 respectively. Thus, vitamin A favored the SPE phase over the micellar phase in the distribution analysis. In vivo absorption experiments with SPE and non-SPE perfusates showed decreased net vitamin A absorption rates in the presence of SPE by 8.7% Thus, dietary ingestion of SPE results in some impairment of intestinal absorption of vitamin A, and may require vitamin A supplementation.

Animals↗

First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model.

The aim of this study in pigs was to investigate the local pharmacokinetics of fexofenadine in the intestine and liver by using the pig as a model for drug transport in the entero-hepatobiliary system. A parallel group design included seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a jejunal single-pass perfusion combined with sampling from the bile duct and the portal, hepatic, and superior caval veins was performed. Fexofenadine was perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000 mg/l, total dose 200 mg). The animals were fully anesthetized and monitored throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/- S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/- 0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or biliary clearance. The E(H) for verapamil and antipyrine agreed well with human in vivo data. Verapamil did not increase the intestinal absorption of fexofenadine, even though the jejunal permeability of fexofenadine, verapamil, and antipyrine showed a tendency to increase in G2. This combined perfusion and hepatobiliary sampling method showed that verapamil did not affect the transport of fexofenadine in the intestine or liver. In this model the E(H) values for both verapamil and antipyrine were similar to the corresponding values in vivo in humans.

Animals↗

Changes in intestinal absorption of 5-fluorouracil-treated rats.

5-Fluorouracil chemotherapy is often accompanied by gastrointestinal toxicity. In this study, we investigated the effect of 5-fluorouracil on the epithelial barrier function of rat small intestine by examining the absorption of a poorly absorbable marker, fluorescein isothiocyanate-labelled dextran (molecular weight 4,400). We further evaluated the intestinal absorption of 5-fluorouracil in rats treated orally with 5-fluorouracil once daily for 4 days. The small intestinal absorption of fluorescein isothiocyanate-labelled dextran and 5-fluorouracil was tested using in situ closed loop intestine technique and in vitro everted intestine technique, respectively. After administration of 5-fluorouracil to rats for 4 days, the body weight of rats decreased significantly and the fluorescein isothiocyanate-labelled dextran concentration in plasma increased significantly, compared with that of control rats to which the saline solution alone was administered. Moreover, the intestinal absorption of 5-fluorouracil in the 5-fluorouracil-treated rats was enhanced significantly, compared with that of control rats. The administration of 5-fluorouracil to rats caused body weight loss and epithelial barrier dysfunction of the small intestine in rats as shown by the increased permeation of the high molecular weight compound, fluorescein isothiocyanate-labelled dextran. The increased absorption of 5-fluorouracil after this treatment suggest that the 5-fluorouracil toxicity might be amplified by its treatment.

Animals↗

Magnesium and potassium deprivation and supplementation in animals and man: aspects in view of intestinal absorption.

States of K and Mg deficiency, deprivation or depletion, are difficult to detect by determining serum concentrations, since both cations are concentrated intracellularly. The intestinal absorption of K is rather quick and complete; the uptake of Mg probably comprises two mechanisms and proceeds continuously, although incomplete. The resulting different pharmakokinetic behavior must be kept in mind when K and Mg are supplemented by the oral route. Favorable effects of oral K and Mg supplementation are reviewed, and the fact is stressed that the body cannot retain K, unless the Mg status is adequate. Therefore, K should be supplemented together with Mg. Drugs like amiloride not only spare K, but at the same time prevent renal losses of other important electrolytes, especially of chloride and Mg.

Administration, Oral↗

Intestinal absorption of aluminium in rats.

To study the mechanism of intestinal aluminium (Al) absorption, an experimental investigation into the uptake of Al from the rat gut was undertaken. The small intestine was perfused in situ for 60 min with isotonic media containing 4.63, 9.25, and 18.50 mmol/l Al chloride at pH 4.0 and 7.0. Portal and systemic blood were sampled and analysed for its Al content by flameless atomic absorption spectrophotometry. It was found that the intestinal absorption of Al in rats is concentration and pH dependent.

Aluminum↗

[Intestinal absorption of homologous and heterologous immunoglobulin G in newborn calves].

Studying the prophylactic effects of specific yolk antibodies against diarrhea in newborn calves, also the intestinal absorption of unspecific heterogeneous avian antibodies as well as their effects on the uptake of maternal bovine colostral antibodies (bIgG) was investigated. Two groups of newborn calves received egg powder (16 g or 8 g per day) for the first 10 days of their life beginning with the first meal. A third group was kept as a control without any egg powder in their diet. Blood samples (5 to 10 calves per sampling time) were taken from 123 calves at 6, 12, 24, 48, or 96 h postnatally. With both doses the highest chicken IgG (cIgG) levels (3.1 micrograms resp. 1.2 micrograms per ml serum) have been measured 12 h after birth. These concentrations decreased continuously to the levels of 1.1 micrograms resp. 0.2 micrograms cIgG per ml serum at 96 h postnatally. The uptake into blood at 6 h postnatally has roughly been estimated as approximately 23% (bIgG) and 7% resp. 6% (cIgG) of the IgG dosages given with the first meal. The time-course (6 to 96 h) of the bIgG level in blood was quite stable, plateauing already after 6 h at a mean of 5.9 mg per ml serum. Significant differences between the bIgG levels of calves with yolk antibodies in their diet (6.2 resp. 6.1 mg bIgG per ml serum) and those of the control group (5.4 mg per ml serum) could not be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Intestinal absorptive capacity of glucose, Na+, K+ C++ and Cl-, in vivo in Cotugnia polyacantha infected dove.

The absorptive capacity of the intestine of dove infected by the cestode Cotugnia Polyacantha was studied by the in vivo perfusion technique. The two glucose concentrations 5 and 27 mM were used in the perfusion fluid. Glucose was added at the expense of Nacl to the total osmolarity 238 mOsmol./L. The perfusion fluid of 5 mM glucose: the percentage of reduction in the absorptive capacity in the infected intestine than normal was (at initial pH7) 82.8, 63.1, 68.4, 71.2 and 67.5 and (at initial pH6) 89.7, 59.0, 70.3, 59.9 and 62.6 in glucose, Na+, K+, Ca++ and Cl- respectively. The perfusion fluid of 27 mM glucose: the percentage of reduction in the absorptive capacity in the infected intestine than normal was (at initial pH6) 89.7, 59.0, 70.3, 59.9 and 62.6 in glucose, Na+, K+, Ca++ and Cl- respectively. The perfusion fluid of 27 mM glucose: the percentage of reduction in the absorptive capacity in the infected intestine than normal was (at initial pH7) 85.6, 65.6, 68.3, 71.1 and 66.9 (at initial pH6), 86.1, 62.4, 70.2, 66.4 and 68.8 in glucose, Na+, K+, Ca++ and Cl- respectively. The wet and dry weight of both tunica muscularis and mucosa were increased in the infected part of intestine than normal.

Animals↗

Relationships between intestinal absorption and hemodynamics.

There are many interactions between intestinal blood flow and absorption. These include the support of transcellular transport by O2 delivery; the passive effects of Starling forces on absorption, secretion, and mucosal conductance; the washout of absorbed materials; and countercurrent exchange. Blood flow hemodynamics, and absorption interact. Regulatory mechanisms add a tertiary influence to these interactions. Further progress in this area would be greatly helped by techniques that could measure blood flow and hemodynamic factors at the absorptive and secretory sites more precisely.

Animals↗

Intestinal absorption of medium chain fatty acids: in vivo studies in pigs devoid of exocrine pancreatic secretion.

In order to study the influence of pancreatic enzyme secretion on the intestinal absorption of medium-chain fatty acids (MCFA), three growing pigs (mean body-weight 61 kg) with ligated and severed pancreatic ducts were fitted with a permanent fistula in the duodenum and with two catheters in the portal vein and carotid artery respectively. An electromagnetic flow probe was also set up around the portal vein. A mixture of octanoic and decanoic acids, esterified as medium-chain triacylglycerols, together with maltose dextrine and nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the two vessels at regular intervals of time for 8 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentrations of non-esterified octanoic and decanoic acid in the portal blood increased slowly after the beginning of each infusion, reaching about 10 times higher values than the basal level. Only 26% of octanoic acid infused in the duodenum and 27% of decanoic acid were recovered in the portal flow throughout each experiment. The possible mechanisms underlying the appearance of MCFA in the portal blood in the absence of pancreatic enzyme secretions and the importance of duodenal absorption of MCT in such physiological conditions have been discussed.

Animals↗

A method of studying the intestinal absorption of aluminium in the rat.

Aluminium (Al) intoxication in dialysis patients is held to be caused not only by Al in the dialysis fluid but also by Al from orally administered phosphate binders. Studies on Al absorption in patients and healthy individuals as well as in animals are still scarce, and do not provide sufficient data to characterize the absorption process. This paper presents a method of studying the process of Al absorption in a perfusion system of rat small intestine in vivo, in combination with a cannulation system of the portal vein for serial blood sampling. Determination of concentrations of an absorbed substance in samples of both the perfusion medium and the portal blood, collected during the perfusion medium and the portal blood, collected during the perfusion period, may clarify the nature of the absorption process. Although this method appears to be useful for the study of the intestinal absorption of any substance, it was adapted for the study of the intestinal absorption of Al compounds. The usefulness of this method for studying Al absorption was demonstrated in an experiment in which Al chloride (0.5 g/l) in buffered media of pH 7.0, 7.5, and 8.0 was perfused through the rat small intestine over a period of at least 30 min. The results of this experiment indicate that a decrease in pH of the perfusion medium leads to an increase in absorption of Al in the portal blood.

Aluminum↗

Effect of PUVA on intestinal calcium absorption.

Intestinal calcium absorption increased significantly following 14 days of treatment with photochemotherapy (PUVA) in seven patients with chronic psoriasis. Irradiation with UVA alone over a similar period did not result in significant changes in calcium absorption in an additional seven psoriatic patients. These findings suggest that the increase in serum 25-OH vitamin D levels previously reported in patients treated by PUVA may have important biological consequences.

Aged↗

[Influence of picolinic acid and citric acid on intestinal absorption of zinc in vitro and in vivo].

The influence of the ligands picolinic acid and citric acid on the intestinal absorption of zinc was studied in two different experimental trials with Zn-depleted and Zn-supplied pair-fed rats using everted sacs in vitro and the ligated small intestine in vivo. ZnSO4 was applied in water solution (pH 5.8) without ligands or together with picolinic acid at a molar ratio of 1:0.2, 1:2, and 1:20 or together with citric acid at a molar ratio of 1:1, 1:10, and 1:100. The intestinal Zn transfer of the Zn-depleted rats with picolinic acid is significantly increased only at a molar ratio of 1:20 (zinc:ligand) (P less than 0.001). The other in vitro results of Zn absorption were only slightly improved, mainly at the high molar excess of picolinic acid in comparison to ZnSO4 without ligands. Only a tendency for an increased Zn transfer--however, already at a narrow molar ratio of 1:1 or 1:10--could be seen when citric acid was added. The intestinal uptake was not influenced by citric acid. The absorption of zinc in vivo did not vary in dependence of the addition of picolinic or citric acid in different molar ratio in comparison to ZnSO4 addition without ligands. Zn-depleted rats showed a significantly higher Zn absorption rate than Zn supplied pair-fed rats independently of the kind of ligand and the zinc:ligand ratio (P less than 0.001). These results are discussed in detail.

Animals↗

Lack of influence of etretinate on the intestinal absorption of D-xylose and of phytomenadione (vitamin K1) as representatives of hydrophilic and lipophilic compounds.

The possible influence of the aromatic retinoid etretinate (Tigason ) on the intestinal absorption of D-xylose and phytomenadione (vitamin K1) has been studied in 7 healthy male volunteers between 22 and 25 years of age. D-xylose and phytomenadione were selected as being representative of water-soluble and fat-soluble test compounds, respectively. Following an oral dose of 25 g D-xylose the plasma levels and urinary excretion pattern of the compound were followed over 6 h. The plasma concentrations of phytomenadione after an oral dose of 20 mg of the vitamin were measured over 14 h. These absorption tests were performed before (baseline) and at the end of a 3-week treatment period with 25 mg b.i.d. etretinate. In addition some parameters on the serum lipid status pre and post etretinate treatment were monitored. The pharmacokinetic and biochemical determinants after treatment with etretinate were referenced to the pretreatment values and nonparametric confidence intervals (a less than 0.05) for these ratios were calculated. With respect to the area, AUC, under the D-xylose plasma concentration--time curve (0.79 less than or equal to RAUC = 1.00 less than or equal to 1.17) as well as to the cumulative amount excreted into urine over 6 h (0.90 less than or equal to RSUM = 1.04 less than or equal to 1.28) and to renal clearance (0.91 less than or equal to Rcl = 1.05 less than or equal to 1.25), no effect of etretinate on absorption and/or renal handling of D-xylose was discernible.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects.

UNLABELLED: Suboptimal gastrointestinal absorption is a problem for many direct thrombin inhibitors. The studies presented herein describe the new oral direct thrombin inhibitor H 376/95, a prodrug with two protecting residues added to the direct thrombin inhibitor melagatran. Absorption properties in vitro: H 376/95 is uncharged at intestinal pH while melagatran is charged. H 376/95 is 170 times more lipophilic (octanol water partition coefficient) than melagatran. As a result, the permeability coefficient across cultured epithelial Caco-2 cells is 80 times higher for H 376/95 than for melagtran. Pharmacokinetic studies in healthy volunteers: H 376/95 is converted to melagatran in man. Oral bioavailability, measured as melagatran in plasma, is about 20% after oral administration of H 376/95, which is 2.7-5.5 times higher than after oral administration of melagatran. The variability in the area under the drug plasma concentration vs. time curve (AUC) is much smaller with oral H 376/95 (coefficient of variation 20%) than with oral melagatran (coefficient of variation 38%). Pharmacodynamic properties: H 376/95 is inactive towards human alpha-thrombin compared with melagatran [inhibition constant (K(i)) ratio, 185 times], a potential advantage for patients with silent gastrointestinal bleeding. In an experimental thrombosis model in the rat, oral H 376/95 was more effective than the subcutaneous low molecular weight heparin dalteparin in preventing thrombosis. CONCLUSION: By the use of the prodrug principle, H 376/95 endows the direct thrombin inhibitor melagatran with pharmacokinetic properties required for oral administration without compromising the promising pharmacodynamic properties of melagatran.

Administration, Oral↗

Intestinal absorption and biliary secretion of zinc in rats with chronic renal failure.

BACKGROUND/AIMS: In chronic renal failure (CRF), zinc deficiency is partially attributed to decreased intestinal zinc absorption, but the mechanism of this decrease in intestinal zinc absorption is obscure. Therefore, the objective of this study was to investigate the cause of decreased intestinal zinc absorption in a uremic rat model using an in vivo perfusion technique as well as to evaluate the effect of intestinal zinc perfusion on the secretion of biliary zinc in normal and CRF rats. METHODS: CRF was induced by five-sixths nephrectomy (Nx). During zinc sulfate perfusion, absorption of zinc in the small intestine and the response of plasma zinc level were measured. After intestinal zinc perfusion for 80 min, the concentrations of zinc and metallothionein (MT) in the intestinal mucosal and liver tissue were assayed. The secretion of biliary zinc and the excretion of urinary zinc were also determined before and after zinc sulfate perfusion. The results were compared with those obtained from 10 sham-operated normal rats. RESULTS: The CRF rats showed a significant decrease in the rate of intestinal zinc absorption and in the response of plasma zinc levels during intestinal zinc perfusion. They also had significantly higher levels of mucosal zinc and MT than sham-operated normal rats, but their contents of liver zinc were significantly lower than those of sham-operated normal rats after zinc sulfate perfusion. CRF rats showed a low plasma zinc level and a high urinary zinc excretion in baseline levels, but had similar output of basal biliary zinc as compared with sham-operated normal rats. Zinc sulfate perfusion in the small intestinal was not found to increase the secretion of biliary zinc and the excretion of urinary zinc, either in normal or CRF rats. CONCLUSION: In the CRF rat, the reduction of intestinal zinc absorption may result from reduced mucosal zinc efflux from the basolateral membrane into plasma. These data also suggest that the absorbed zinc from the gastrointestinal tract is mostly taken up by the liver or other tissues, and is less excreted in bile juice and urine.

Animals↗

The acute effect of sodium cellulose phosphate on intestinal absorption and urinary excretion of calcium in man.

Intestinal 47Ca absorption has been determined from blood and stool radioactivity after oral administration of the isotope in nine patients before and during cellulose phosphate treatment. Oral administration of 5 g cellulose phosphate concomitant with 47Ca in 100 mg "carrier" calcium as CaCl2 decreased 47Ca absorption by 80 per cent. Cellulose phosphate, 5 g three times daily, decreased urinary excretion of non-radioactive calcium by 47 percent. Urinary magnesium excretion decreased by 47 percent whereas urinary phosphorus excretion increased by 67%. Calcium and magnesium excretion in urine decrease because cellulose phosphate binds divalent cations within the GI tract. The increased phosphorus excretion is probably due to partial hydrolysis of the substance in the gut.

Calcium↗

Effects of salicylate on intestinal absorption: in vitro and in vivo studies with enterotoxigenic micro-organisms.

This study was done to determine whether salicylate could affect alterations in intestinal absorption induced by preparations of enterotoxigenic micro-organisms. It was found in rats that salicylate increased intestinal monosaccharide uptake in vitro and reversed the inhibitory effects induced by cell-free preparations of Staphylococcus sp., Candida sp. and Klebsiella sp. In vivo, salicylates increased net water absorption in rat jejunum exposed to cell-free preparations of various micro-organisms. Increase in net fluid flux occurred after subcutaneous injection only with bacteria which stimulate adenylate cyclase activity. These observations suggest that the absorptive and anti-secretory effects of aspirin are cyclic nucleotide dependent. The potential clinical role of salicylates as anti-secretory agents in diarrhoeal diseases, particularly in children, requires further investigation.

Animals↗