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PubMed1977

[Intestinal absorption of digoxin in systemic sclerosis (author's transl)].

Gastro-intestinal absorption of digoxin was evaluated in 18 patients with progressive systemic sclerosis. In 8 patients a single-dose crossover study was performed after oral and intravenous administration of 0.5 mg digoxin by comparing the aera under the eight-hour plasma concentration curve. The fraction of the dose absorbed was diminished in 4 patients to less than 55%. There was a significant positive correlation between the extent of digoxin absorption and xylose renal excretion. In addition, steady state digoxin plasma levels and 24-h urinary excretion of digoxin were determined during maintenance therapy in 12 patients. In 6 patients renal excretion of digoxin was clearly less than in normal subjects during chronic dosing of the same digoxin preparation. This finding corresponded well with digoxin plasma levels below the usual therapeutic range in most of the patients. The impaired absorption of digoxin failed to correlate with the extent of the skin manifestation or the time course of the disease while there was massive oesophageal dysfunction in most of these patients. The results suggest that an inadequate therapeutic response to cardiac glycosides in patients suffering from progressive systemic sclerosis is at least partially due to impaired digoxin absorption. Similar problems could occur in therapy of the disease itself due to insufficient enteral absorption of drugs used in treatment of systemic sclerosis.

Administration, Oral↗
PubMed1980

Effect of raw legume diets on intestinal absorption of D-galactose by chick.

The effect of four raw legume diets on the intestinal absorption of D-galactose and oxygen consumption were studied in chick. Field beans (Vicia faba), soybeans (Glycine soja), bitter vetch (Vicia ervilia), and navy beans (Phaseolus vulgaris), were used. The intestinal absorption was determined by both in vivo and in vitro techniques. In vivo, only navy beans and soybeans inhibit intestinal transport of D-galactose, while in vitro all the diets do. Oxygen consumption by intestinal rings increases in chicks fed on bitter vetch diet.

Animal Feed↗
PubMed2000

Intestinal absorption and biliary secretion of 5MTHF: effect of ethanol.

The aim of this work was to study intestinal absorption, using the whole intestine in vivo with 5-methyltetrahydrofolate (5MTHF), and the subsequent appearance of this compound in the bile, in control and in ethanol-fed rats. The ethanol-fed rats drank ethanol (5 to 30% vol/vol) in tap water for 5 wk. A consumption of 30% was maintained in this group for 20 additional weeks. The two groups of rats were cannulated at the beginning and at the end of the intestine. Three solutions containing 0.5, 1.0, and 2.5 microM of cold 5MTHF and 14C-methyltetrahydrofolic acid (0.01 microCi/mL) in each were perfused throughout the intestine at a flow rate of 4.5 mL/min. The absorption of folate was calculated from the difference between concentrations at the beginning and at the end of the perfusion. A decrease in 5MTHF uptake was observed at the concentration of 1.0 microM (p<0.05): however, folate absorption was not significantly modified at 0.5 and 2.5 microM in the perfusate. Serum folate levels were significantly lower in the ethanol-fed rat group. This fact could be due to a lower intake of folate in the diet and/or to the effect of alcohol on the intestinal absorption. The bile duct was isolated and cannulated with a polyethylene cathether. No significant differences were noted in the biliary folates between the control and the ethanol-fed rats.

Animals↗
PubMed1996

Intestinal absorption of sugar-coupled somatostatin analogs.

The intestinal absorption of glycosylated somatostatin analogs was compared in rat enterocyte brush border membranes as an in vitro test system and rats as an in situ absorption model. Derivatives of the cyclic octapeptide octreotide with mono-, di-, and trisaccharide residues were used. The uptake of octreotide by the vesicles was inhibited by the glycosylated analogs. The uptake was not inhibited by the bicyclic octapeptide alpha-amanitin, which exhibits structural similarity but is not absorbed in rats. The inhibition of octreotide permeation into the vesicles decreased in the presence of derivatives with an increasing length of the carbohydrate residues. To evaluate, whether the vesicle system is predictable for the in situ situation, the extent of absorption of the peptides was determined after intrajejunal administration. A linear relationship between inhibitory capacity of the octreotide derivatives in the vesicle system and their in situ absorption efficiency was found when blood was taken from a mesenteric vein. However, after sampling from a peripheral vein, deviations from the predicted values were noted. These differences reflected changes in pharmacokinetics (e.g., hepatic elimination) rather than in absorption. In summary, the data indicate that the vesicle system is a useful tool to predict the absorption efficiency of glycosylated somatostatin analogs in situ.

Animals↗
PubMed1979

Intestinal absorption under the influence of vasopressin: studies in unanaesthetised rats.

Experiments were carried out in different segments of the intestine of unanaesthetised rats to assess the effect of vasopressin on intestinal absorptive processes. The following data were observed. (1) Within a physiological range of doses (Aziz, 1969), ADH diminished the net sodium absorption mainly by reducing the unidirectional sodium influx, whereas the behaviour of the efflux was not uniform. (2) The unidirectional volume fluxes showed the same behaviour as did the sodium fluxes. (3) ADH produced an oral-aboral gradient (jejunum greater than ileum greater than colon). (4) ADH did not significantly change the transfer of actively transported sugars; it did influence, however, passively transported substances. (5) During the intravenous application of ADH, a substance was secreted into the perfusion solution which diminished the absorption of volume and electrolytes. (6) Cyclic AMP acted on intestinal absorption in the same way as did ADH. In view of these results two mutually independent transport pathways for sodium and water are supposed, one of which is influenced by ADH or cAMP. Based on a two membrane model, an ADH mechanism is discussed: the permeability of the luminal membrane system is enhanced in the presence of vasopressin.

Animals↗
PubMed1997

Small-intestinal absorption of cadmium and the significance of mucosal metallothionein.

1 Although food intake is among the most important routes of Cd exposure, not many details are known about the intestinal absorption mechanisms of Cd. In this respect Cd is representative of most other nonessential, merely toxic metals. 2 Based on a concept of two distinguishable steps, intestinal absorption of Cd is characterized by high accumulation within the intestinal mucosa and a low rate of diffusive transfer into the organism. 3 After uptake into the mammalian organism, Cd is sequestered into hepatic metallothionein (MT). It is assumed that hepatic Cd-MT then gradually redistributes Cd to the kidney, which is the main target organ for chronic Cd toxicity. 4 When feeding low levels of dietary CdCl2, however, Cd accumulates preferentially in the kidney and to a lesser degree in the liver, a distribution pattern also found after intravenous and peroral administration of the Cd-MT complex itself. As dietary Cd induces intestinal MT, intestinal Cd-MT complexes could be at least partly responsible for the renal accumulation of dietary Cd. 5 For this mechanism, however, serosal release of mucosal Cd-MT is required. In fact, in vitro findings in rats reveal a concentration-dependent release of intestinal MT to the serosal side of the small intestine. These results indicate that endogenous intestinal MT may deliver Cd-MT to other inner organs, thus contributing to the preferential renal accumulation of ingested Cd.

Animals↗
PubMed1977

Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport.

Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length.

Animals↗
PubMed1976

Intestinal absorption, demethylation, and enterohepatic circulation of imipramine.

The intestinal absorption and metabolism of single oral doses of imipramine (ip) have been studied in man by portal catheterization. The concentration of ip and the formed desipramine (dmi) was followed in blood-plasma obtained from the portal and cubital veins. The absorption of ip seemed to be completed 80 min after the administration of the drug. There was no sign of demethylation of ip during the passage across the intestinal wall. Evidence was found of an enterohepatic circulation of both ip and dmi.

Dealkylation↗
PubMed1994

Comparative effects of intestinal absorption of folic acid and methyltetrahydrofolic acid in chronic ethanol-fed rats.

This study concerns in vivo folic acid and methyltetrahydrofolic acid (MTHF) absorption by the whole intestinal surface after 20 weeks of 30% ethanol ingestion in drinking water. The results were compared with control rats fed ad libitum. The total intestinal serosal areas were similar in ethanol-fed and control rats. Significant increases in intestinal length, and decreases in tissue wet and dry weights were found in ethanol-fed rats. Serum folic acid concentrations were significantly less in the animals which had ingested ethanol than in the control rats. Intestinal folic acid absorption was significantly increased at lower substrate concentrations (0.5 and 1 microM), while no difference was observed at 2.5 microM in the ethanol-fed rats. Folic acid absorption relative to tissue wet weight showed significant increases at all tested concentrations in the ethanol-fed rats. Intestinal MTHF absorption showed no significant changes at 0.5 microM MTHF concentration, and an increase was observed in the absorption values at 1 and 2.5 microM concentrations in the ethanol-fed rats. When expressed as tissue wet weight, MTHF absorption values in ethanol-fed rats increased at 1 and 2.5 microM but did not differ at 0.5 microM substrate concentrations. The above results indicate compensatory responses in the folic acid and MTHF intestinal absorption after chronic ethanol ingestion. These effects are observed when the whole intestinal surface is evaluated.

Animals↗
PubMed1982

Acute effects of guar gum on glucose tolerance and intestinal absorption of nutrients in rats.

The mechanism by which non-digestible fibres improve oral glucose tolerance is still unclear. We have studied the effects of guar gum on oral carbohydrate tolerance and intestinal absorption of nutrients in anaesthetized rats. Addition of guar to an intragastric glucose load (1 g/kg) markedly delayed the rise in plasma glucose levels when the concentration of the gum was adequate (10 mg/ml). The insulin response was somewhat less marked, but the differences were not significant. When glucose was introduced directly into the duodenum, the gum only slightly reduced the rise in glucose levels, during the first 15 min. If sucrose (1 g/kg) was infused in the duodenum, acarboseR, an alpha-glucosidase inhibitor, but not guar, slowed the rise in plasma glucose and insulin levels. Intestinal absorption was measured in a tied duodenojejunal loop. Guar decreased active transport of glucose (4 mmol/l) by approximately 20%, but had no significant effect on the passive transport of glucose (100 mmol/l), nor on the absorption of sucrose (40 mmol/l) or leucine (4 mmol/l). At the concentration which improved glucose tolerance (10 mg/ml), but not at lower concentrations, guar gum markedly slowed gastric emptying. These results suggest that guar gum improves tolerance to oral carbohydrates mainly by decreasing the rate of gastric emptying, but inhibition of intestinal absorption may also be involved in the presence of low concentrations of the sugars.

Animals↗
PubMed1969

Early stages of intestinal absorption of specific antibiodies in the newborn. An ultrastructural, cytochemical, and immunological study in the pig, rat, and rabbit.

In mammals, passive immunity is transferred from mother to offspring by transplacental passage or by intestinal absorption. The rabbit receives antibodies exclusively across the placenta, whereas intestinal absorption is the principal source of antibodies for the new-born pig. In the rat, passive immunity is transferred by both pathways. The role of the jejunal absorptive cells was investigated in these three species, by the use of specific immune globulins as tracers of protein absorption. Rabbit anti-peroxidase and anti-ferritin antibodies were injected into the jejunum of newborn pigs, rats, and rabbits, and absorption was studied over the first 2 hr. The specific antibodies were detected in glutaraldehyde-fixed tissues after in vitro treatment with the antigens, and in sera by immunological methods. Intact antibodies are transferred into the circulation of the pig and the rat, but not into that of the rabbit. In the three species, the jejunal absorptive cells take up antibodies by endocytosis. In the pig, the antibodies are transported across the epithelium in vacuoles. In the rabbit, the endocytosis of antibodies triggers a lysosomal response and all absorbed antibodies are trapped in lysosomes. In the rat, both situations are found; there is no evidence of transfer of antibody fragments into the circulation.

Animals↗
PubMed1990

Effect of verapamil on intestinal absorption of calcium in the rat.

The effect of verapamil in vitro, and the in vivo effect of both oral and parenteral verapamil administration on intestinal absorption was tested using everted gut sacs of duodenum, jejunum, distal ileum and proximal colon in rats. In the in vivo study, the effect of verapamil on blood levels of calcium, phosphorus and 1.25(OH)2D3, was investigated and a complete calcium balance was performed. In vitro, verapamil (1.5 mM) inhibited calcium absorption by the duodenum and colon only. Oral verapamil led to a reduction in the blood level of 1.25(OH)2D3. However, both oral and parenteral verapamil had no effect on the intestinal absorption, urinary secretion and consequently on the calcium balance.

Animals↗
PubMed1984

Effect of phosphate on the intestinal absorption of lead (203Pb) in chicks.

The effect of phosphate on the intestinal absorption of lead (203Pb2+) was examined in chicks. Absorption was determined by the in situ ligated duodenal loop technique. In one approach, diets differing in phosphate content were fed to 2-week-old chicks for a period of 7 days. With respect to the control group (1.06% P), a severe phosphate deficiency (0.16% P) decreased growth, CaBP synthesis and 203Pb absorption; a moderate phosphate deficiency (0.33% P) resulted in an increase in CaBP production and 203Pb absorption; and the high phosphate diet (2.12%) gave mean values for CaBP synthesis and 203Pb absorption intermediate between those from the chicks fed the 0.33 and 1.06% diets. 203Pb absorption was highly correlated with CaBP concentrations. In another approach, phosphate in varying concentrations was added directly to the dosing solution. In one study, phosphate addition (0.1 mM) depressed 203Pb absorption in rachitic and cholecalciferol-treated chicks. When the data were expressed in terms of absorption of the soluble 203Pb present in the intestinal lumen at the end of the absorption period, an effect of phosphate in addition to the precipitation of the insoluble lead salt was uncovered. In an experiment with normal chicks, it was observed that phosphate in the dosing solution at concentrations of 1 and 2 mM partially and significantly reversed the inhibitory effect of lower concentrations of phosphate (0.01 mM and 0.1 mM). These data demonstrate the complexity of the phosphate-lead interaction, in addition to directly showing an effect of dietary phosphate on intestinal lead absorption.

Animals↗
PubMed1976

Intestinal absorption of beta-alanine, anserine and carnosine in rats.

Absorption beta-alanine, anserine or carnosine from rat intestine was studied in vivo by a force feeding method and in vitro using an everted sac method. Possibility of anserine and carnosine hydrolysis prior to intestinal absorption was also investigated using a glycylleucine dipeptidase-containing fraction prepared from rat intestine. The following results were obtained. 1) Anserine and carnosine were absorbed as they were from rat small intestine. 2) Both anserine and carnosine were partially hydrolyzed in vitro by the glycylleucine dipeptidase-containing fraction. Carnosine was hydrolyzed faster than anserine. The above rather conflicting results suggest that physiological amounts of anserine and carnosine might be absorbed from rat small intestine in dipeptide forms.

Alanine↗
PubMed1997

Intestinal transport and metabolism of analgesic dipeptide, kyotorphin: rate-limiting factor in intestinal absorption of peptide as drug.

Intestinal transport and metabolism of kyotorphin (KTP) were studied in rat everted small intestine. KTP on the mucosal side was metabolized completely within 60 min, and any amounts of KTP were not detected on the serosal side. On the other hand, [D-Arg2]-KTP (D-KTP) was stable on the mucosal side to appear on the serosal side. However, N-t-butoxycarbonyl-KTP (Boc-KTP), which was metabolized on the mucosal side faster than KTP, appeared on the serosal side. In intestinal homogenate, KTP was metabolized, and the metabolic clearance (CL(met)) was decreased by peptidase inhibitors, bestatin, o-phenanthrolin and tryptophan hydroxamate. In the presence of these peptidase inhibitors, the absorption clearance (CL(abs)) of KTP was increased. The less the CL(met) of KTP was, the more the CL(abs) of KTP was. Meanwhile, Boc-KTP in intestinal homogenate was stable even in the absence of peptidase inhibitors. The CL(abs) of Boc-KTP was constant irrespective of the stability on the mucosal side. Kinetic analysis by the metabolic inhibition model indicated that the stabilization of KTP in the intestinal tissue could increase the CL(abs) up to 0.247 microl/min per cm, which was as much as the CL(abs) of stable D-KTP. These results led to the conclusion that rate-limiting process in intestinal absorption of KTP is metabolic degradation in intestinal tissue during the absorption.

Analgesics↗
PubMed1997

Some technical precisions to a method for in vivo intestinal absorption studies.

Some modifications to the method of PONZ et al. for in vivo intestinal absorption studies using an in situ perfused segment of small intestine, under anesthesia, are described. They improve its accuracy and applicability, especially when slowly absorbed substrates are used or when volume flux measurements are desired. Calculations for the absorbed substrate and net fluid volume change determinations are reported. Several aspects of the use of the method under a single pass or a recirculation perfusion system are discussed.

Animals↗
PubMed1975

Effects of normal alcohols on intestinal absorption of salicylic acid, sulfapyridine, and prednisolone in rats.

The rates of intestinal absorption of salicyclic acid, sulfapyridine, and prednisolone from solutions containing no alcohol or 0.5% ethanol, n-butanol, or n-hexanol were determined. At the concentrations used, ethanol did not significantly affect drug absorption. Butanol reduced the rate of absorption of sulfapyridine but did not significantly affect the absorption rates of prednisolone or salicylic acid. Hexanol reduced the rates of absorption of sulfapyridine and salicylic acid and increased the rate of absorption of prednisolone. The absorption-altering effects of the alcohols were concentration dependent and rapidly reversible. Histological studies indicated that the structure of the epithelium was not altered by the alcohols. While the absorption rate of water from the drug solutions was increased by the alcohols, their absorption-altering effects could not be attributed solely to increased water flux. In addition, the absorption-altering effects of the alcohols could not be attributed to formation of drug-alcohol complexes nor to alcohol-induced alterations in the extent of binding of the drugs to nondialyzable materials in the intestinal drug solution.

Alcohols↗