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PubMed2000

Adaptation in iron absorption: iron supplementation reduces nonheme-iron but not heme-iron absorption from food.

BACKGROUND: Results of cross-sectional studies suggest that in healthy people, iron absorption adapts to meet physiologic needs and stabilize iron stores, but this has not been adequately tested in longitudinal studies. OBJECTIVE: We tested whether heme- and nonheme-iron absorption decrease in response to increased iron intake and whether iron stores reach a steady state. DESIGN: In a randomized, placebo-controlled trial, heme- and nonheme-iron absorption by healthy men and women (n = 57) were measured before and after 12 wk of supplementation with 50 mg Fe/d as ferrous sulfate. Serum and fecal ferritin were measured during supplementation and for 6 mo thereafter. RESULTS: Initially, both heme- and nonheme-iron absorption were inversely associated with serum ferritin concentration. Volunteers who took iron supplements, even those with serum ferritin <21 microg/L (n = 5), adapted to absorb less nonheme iron (3.2% at week 12 compared with 5.0% at week 0, P: < 0.001) but not less heme iron from a beef-based meal. Serum ferritin concentration was slightly but significantly higher after iron supplementation than after placebo (difference = 13 microg/L). This higher ferritin concentration persisted for >/=6 mo after supplementation, except in subjects with low iron stores, whose serum ferritin returned to baseline within 3 mo. Fecal ferritin excretion increased 2.5-fold (P: < 0.05) during supplementation. CONCLUSIONS: Healthy individuals, even those with low iron stores, had reduced nonheme-iron absorption from food in response to iron supplementation. Despite this partial adaptation, iron stores were greater after iron supplementation than after placebo and this difference was sustained, except in individuals with the lowest iron stores.

Adaptation, Physiological↗

PubMed1991

Mechanisms of absorption of inorganic mercury from rat small intestine. IV: Effect of chelating agents and cysteine on absorption of mercuric chloride in situ and in vitro.

The effects of chelating agents (citric acid, tartaric acid, penicillamine and ethylenediaminetetraacetic acid) and cysteine on the absorption of HgCl2 were investigated in rats. Perfusion of the small intestine showed that the chelating agents and cysteine decreased the absorption of HgCl2 depending on their stability of constants with Hg2+, under the predominant conditions of water absorption and secretion. The difference in absorption of HgCl2 between both conditions was inversely correlated with their logarithmic stability constant values. These agents decreased the transport of HgCl2 through the everted intestinal wall and the uptake of HgCl2 by the intestinal brush border membrane in a similar manner. From these results, it is suggested that the chelating agents and cysteine decrease the absorption of HgCl2 through the pores of the brush border membrane due to the solvent drag effect.

Animals↗

PubMed1985

The promotion of drug rectal absorption by water absorption.

The promotion of the rectal absorption of antipyrine by sodium taurocholate (TC-Na) or sodium ethylenediaminetetraacetate (EDTA-Na) has been examined by in-situ recirculating perfusion in the rat. These promoters significantly increased water influx, efflux and antipyrine absorption clearance (CLAP). Ouabain treatment significantly reduced the increase in both rectal absorption of drug and water flux. Water absorption dependent on active sodium transport may thus possibly promote the rectal absorption of poorly absorbable drugs.

Animals↗

PubMed1987

Ionic regulation of Na absorption in proximal colon: cation inhibition of electroneutral Na absorption.

Active Na absorption (JNanet) in rabbit proximal colon in vitro is paradoxically stimulated as [Na] in the bathing media is lowered with constant osmolarity. At 140 mM [Na]o, JNanet is -0.6 +/- 0.4 mueq X cm-2 X h-1, whereas at 50 mM [Na]o JNanet is 5.0 +/- 0.7 mueq X cm-2 X h-1, P less than 0.01. JNas----m is a linear function of [Na]o, suggesting a diffusional flux. JNam----s increases almost linearly from 0 to 50 mM [Na]o but then plateaus and actually decreases from 50 to 140 mM [Na]o, consistent with inhibition of an active transport process. Both lithium and Na are equally effective inhibitors of JNanet, whereas choline and mannitol do not block the high rate of JNanet observed in decreased [Na]o. Either gluconate or proprionate replacement of Cl inhibits JNanet. Removal of K or HCO3 does not alter Na absorption. JNanet at lowered [Na]o is electrically silent and is accompanied by increased Cl absorption; it is inhibited by 10(-3) M amiloride and 10(-3) M theophylline but not by 10(-4) M bumetanide. Epinephrine is equally effective at stimulating Na absorption at 50 and 140 mM [Na]; yohimbine does not inhibit JNanet at 50 mM [Na]o. Na gradient experiments are consistent with a predominantly serosal effect of the decreased [Na]o. These results suggest that Na absorption in rabbit proximal colon in vitro is stimulated by decreased [Na]; the effect is cation specific, both Na and Li blocking the stimulatory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1978

Volume absorption in the pars recta. III. Luminal hypotonicity as a driving force for isotonic volume absorption.

This paper examines the possibility that osmotic disequilibrium between luminal and bathing solutions may account for isotonic fluid absorption coupled to active Na+ absorption observed when superficial proximal straight tubules isolated from rabbit kidney are perfused and bathed with NaCl solutions in the absence of CO2, HCO3-, and luminal organic solutes. If luminal hypotonicity provides a driving force for isotonic fluid absorption under these conditions, the luminal fluid must be nearly isotonic; and steady-state luminal hypotonicity should develop sufficiently rapidly that the absolute rate of volume absorption ('JV, nl min-1) coupled to active Na+ transport is relatively independent of perfusion rate, so that the normalized rate of fluid absorption (JV, nl min-1 mm-1) is approximately constant. Our theoretical calculations indicate that these expectations are fulfilled. A 0.42-0.56 mM reduction in luminal NaCl concentration adequately accounts for the JV observed under such conditions, because of the high hydraulic conductivity of these tubules; and within the range of tubule lengths normally employed with isolated proximal straight tubules, JV is relatively indepedent of perfusion rate within the generally observed range of experimental error.

Absorption↗

PubMed1976

Absorption of vitamin A in patients with cystic fibrosis. Absorption is best with emulsified vitamin A alcohol.

Vitamin A absorption tests using vitamin A palmitate and alcohol separately in oil and oil-water emulsions were done on 43 patients with cystic fibrosis. Patients were given 7,000 units of vitamin A per kilogram of body weight with a fatty breakfast. Pancreatic enzymes were not given with the test meal and were withheld for five hours from start of test. Blood was drawn before administration of the vitamin and at three and five hours after administration. Serum vitamin A levels were estimated using the Carr-Price technique. The percentages of patients with normal vitamin A absorption were 85 with vitamin A alcohol in oil-water emulsion, 61 with vitamin A alcohol dissolved in oil, 64 with vitamin A palmitate in oil-water emulsion, and 19 with vitamin A palmitate in oil. The number of stools per day is an inverse indicator of retention time in the intestine. Absorption of fat soluble vitamins is always abnormal when a patient has four or more stools a day. The observations that cystic fibrosis patients with abnormal liver biopsies have poor absorption of vitamin A were not statistically significant. The question of the effect of cirrhosis in cystic fibrosis on vitamin A absorption remains unresolved.

Adolescent↗

PubMed1998

Fractional absorption of L-carnitine after oral administration in rats: evaluation of absorption site and dose dependency.

We evaluated the fractional absorption of L-carnitine, a gamma-amino acid essential cofactor for the transfer of long-chain fatty acids, in rats in vivo after oral administration to determine its absorption behavior. At both low (0.05 micromol/rat) and high (100 micromol/rat) doses, L-carnitine was recovered only from the region of the cecum and below at 10 h after administration. During a major shift in distribution from cecum at 10 h to feces at 24 h, there was no significant change in the total recovery at each dose, suggesting that L-carnitine absorption is negligible in the cecum and the large intestine (colon and rectum). However, the recovery of L-carnitine was incomplete and the fraction recovered was larger at the high dose than at the low dose. The fractions absorbed were estimated to be 96.7 and 33.0% for the low and high doses, respectively, as these were the fractions that disappeared from the gastrointestinal tract. These values were comparable with 100 and 42%, respectively, of bioavailability values by the pharmacokinetic analysis of plasma concentration data in our preceding study [Matsuda et al., Biopharmaceutics & Drug Disposition, in press]. These results suggest that L-carnitine is significantly absorbed only in the small intestine, without undergoing first-pass degradation, and in a dose-dependent manner presumably due to the involvement of saturable transport by L-carnitine carriers. Consistent with the suggestions in vivo, L-carnitine absorption in the closed intestinal loop in situ was concentration-dependent in the small intestine but not in the large intestine, and the apparent membrane permeability in the large intestine was smaller by an order of magnitude than that of passive transport in the small intestine. These findings support our preceding kinetic modeling strategy assuming the small intestine to be the sole absorption site, and should be of help in guiding studies on development of more efficient oral L-carnitine delivery strategies.

Administration, Oral↗

PubMed1984

Drug absorption from the gastrointestinal tract and immunity: the mechanism of the decreased absorption of salicylic acid during systemic anaphylaxis. I.

Previous studies have demonstrated the decrease of intestinal salicylic acid absorption in ovalbumin-immunized rats during systemic anaphylaxis. In the present study, the mechanism whereby systemic anaphylaxis interferes with the intestinal absorption of salicylic acid was studied. The pH of the luminal solution was not affected by the intravenous challenge with ovalbumin. A significant increase of the intraluminal protein was observed in rats under systemic anaphylaxis. However, there was no significant difference between ovalbumin-treated rats and saline-treated ones on the binding of salicylic acid with intraluminal macromolecular substances. Enhanced mucus release in the perfusate was also observed in sensitized rats but the extent of decrease in absorption of salicylic acid did not correlate with the increase in amount of the intraluminal mucus in the same animals. In addition, no significant effect was observed on the uptake by the intestinal everted sac of rats with systemic anaphylaxis. These findings suggested that mucus as well as protein is not responsible for the decrease of absorption of salicylic acid induced by systemic anaphylaxis. From these observations, it would appear that the circulatory changes in the gastrointestinal tract may play an important role in the decreased absorption of salicylic acid during systemic anaphylaxis.

Anaphylaxis↗

PubMed1992

Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits.

The absorption of insulin (from porcine pancreas) from the rectum of rabbits after the administration of hollow-type suppositories containing insulin and five kinds of cyclodextrins (CyDs) was investigated. Three types of suppositories were employed: suppository I containing insulin (approximately 26 IU/mg) and various amounts of each CyD in citric buffer solution at pH 3.0 or powder in its cavity, suppository II containing CyD without insulin, and suppository III containing insulin without CyD. Without CyD, the insulin and glucose levels in plasma were unchanged, whereas a significant increase in the plasma insulin concentration and a marked decrease in the glucose levels were found following simultaneous administration of insulin and CyDs by suppository I. The enhancing effect of CyD on rectal insulin absorption (absorption-enhancing effect) by chemically modified CyDs (heptakis(2,6-di-O-methyl)-beta-CyD (DM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD)) was higher than those by natural CyDs (alpha-, beta-, and gamma-CyD). The area under the plasma concentration-time curve (AUC) and Cmax of insulin significantly decreased with the preadministration (administration of CyD 6, 24 and 48 h before rectal insulin administration) of DM-beta-CyD. The absorption-enhancing effect disappeared 24 h after preadministration. These results suggest that CyDs enhance insulin absorption from the rectum, and that attenuation of the membrane transport barrier function in the rectum recovers at a maximum of 24 h after administration of CyDs.

Absorption↗

PubMed1975

Absorption of supplemental iron during pregnancy - a longitudinal study with repeated bone-marrow studies and absorption measurements.

Iron absorption, bone-marrow smears and haematological parameters were repeatedly studied during pregnancy in 50 women. The same studies were repeated two months after delivery. The material was randomly divided into two groups. Twenty-four women were treated with 200 mg of ferrous iron daily while 26 were given placebo. The iron absorption was measured from radioiron-labelled test doses of 100 mg ferrous iron in a whole-body counter with high sensitivity. In the placebo group the iron absorption increased throughout pregnancy from an average of 6.5 % at the 12th week to 14.3 % at the 35th week of gestation. Two months after delivery the absorption was higher than initially. In the iron-treated group the absorption increased between the 24th and 35th week of gestation from 6.0 to 8.6 %. After delivery 5.5 % of the test dose was absorbed. The haemosiderin iron in the bone-marrow was mobilized during pregnancy. In the placebo group no woman had more than trace of haemosiderin in the bone-marrow smears at the 35th week of gestation. In the iron-treated group 65 % had the same bone-marrow findings. The amount of bone-marrow haemosiderin at term seems not to have the same significance for the diagnosis of iron deficiency in pregnancy as in non-pregnant subjects. Two months after delivery about 50 % of the women in the placebo group had restored their iron deposits. In the iron-group the haemosiderin content in the bone-marrow smears was enhanced in most women compared to early pregnancy. In the placebo group haematological data indicated a high frequency of iron deficiency in late pregnancy while in the iron-treated group iron deficiency was prevented.

Adult↗

PubMed1990

Absorption of oral mesalazine-containing preparations and the influence of famotidine on the absorption.

The mesalazine-containing preparations Asacol, Pentasa, and Salofalk (=Claversal) are frequently used in the treatment of inflammatory bowel disease. The release patterns of these formulations are time- and/or pH-dependent. The aim of this study was to investigate the patterns of absorption of these preparations and the influence of raised intragastric pH on absorption. Gastric pH was raised by simultaneous administration of famotidine. Absorption was determined by assaying with a high-performance liquid chromatography method the urinary excretion of acetylmesalazine, the major metabolite of mesalazine. A large intra- and inter-individual variability in absorption was found for all three formulations, both with and without concomitant famotidine administration. Asacol and Pentasa were significantly less absorbed than Salofalk. A significant lower absorption of mesalazine was seen when Asacol was combined with famotidine. Variations in gastric pH have negligible effect on the bioavailability of mesalazine in vivo.

Administration, Oral↗

PubMed1989

Morphologic and functional alterations in absorptive epithelial cells during L-tryptophan induced inhibition of net sodium and fluid absorption in the rat ileum.

L-Tryptophan (L-Trp) has been reported to suppress jejunal fluid and electrolyte transport in vitro, at a 20 mM concentration, whereas other amino acids enhance that absorption at the same concentration. The effect of L-Trp, glycine (Gly) and L-phenylalanine (L-Phe) on in vivo ileal and jejunal fluid and sodium transport, and their morphologic correlates, were investigated in the rat. In the ileum, morphology as well as fluid and sodium transport were more readily altered by L-Trp than in the jejunum. The ileal effects were rapid; morphologic and transport changes were seen within 2.5 minutes. The changes were stereospecific; they occurred only with the levo, but not with the dextro isomer of Trp. There was a concentration dependence; 20 mM levels of L-Trp were required, whereas lower concentrations of the amino acid often stimulated net absorption. Morphologic alterations produced by L-Trp were restricted to absorptive epithelial cells, whereas goblet cells appeared unaffected. Morphologically, L-Trp treatment led to the formation of clear basal vacuoles in ileal absorptive epithelial cells at 2.5 minutes, and extensive vacuolization and loss of the lumenal permeability barrier to macromolecules at 30 minutes. Since L-Trp can be hydroxylated in the small intestine, we assessed the effects of L-5 = OH tryptophan and 5-hydroxytryptamine on small intestinal transport and morphology in this experimental system. L-5-OH tryptophan inhibited fluid transport and produced some epithelial cell vacuolization. However, 5-hydroxytryptamine, which most severely decreased transport, had none of the morphologic effects of L-Trp. We hypothesize that L-Trp may inhibit transport as a result of its intracellular accumulation in absorptive epithelial cells.

Animals↗

PubMedDate not supplied

Absorption of amino acids in isolated pig caecum in situ. Effect of concentration of enzymatic casein hydrolysate on absorption of amino acids.

Absorption of amino acids in isolated pig caecum in situ. Effect of concentration of enzymatic casein hydrolysate on absorption of amino acids. Acta Physiol. Pol., 1978, 29 (1): 67-77. The absorption of amino acids in the pig caecum was studied in situ after surgical isolation of the caecum from the remaining digestive tract and fitting of fistula to the isolated bowel sac. It was found that amino acids can be absorbed in the caecum. Amino acids possessing an additional functional group mainly: asparagine, serine, threonine, tyrosine, arginine, histidine, lysine and aspartic acid, were absorbed while the remaining ten determined amino acids were not absorbed under these conditions. The movement of water across the wall of the caecum and the osmotic pressure in the caecum had no effect on the absorption of amino acids. The absorption of water in the caecum is mainly due to simple diffusion.

Amino Acids↗

PubMed1975

The influence of intestinal absorption of an amino acid on the subsequent absorption of the same amino acid.

Cysteine absorption was determined in an intestinal segment "in situ" in the rat under general anaesthesia, perfusing the segment twice for 30 minutes, at one hour interval, with the same amount of cysteine dissolved in a 0.85% NaCl solution. At the second perfusion, absorption of the amino acid was about half that at the first perfusion. As the first perfusion reduces absorption even in a segment not previously perfused, and intraperitoneal injection of cysteine does not influence absorption, it is postulated that an inhibitory factor, released from the intestinal wall, intervenes by humoral route in the regulating mechanism of the absorption of amino acids.

Amino Acids↗

PubMed1982

Studies on the absorption of practically water-insoluble drugs following injection V: Subcutaneous absorption in rats from solutions in water immiscible oils.

To elucidate the kinetics and mechanisms of subcutaneous absorption of practically water-insoluble drugs in oily solutions, the absorption behaviors of select azo dyes and other prototype agents were investigated by a local clearance method in the dorsum in intact rats. The absorption of the drug components appeared to be first-order. The first-order rate constant (k) was inversely proportional to the cube root of the injection volume. In more limited studies, essentially the same behavior was observed in the rat abdomen, and the difference in k between the dorsal and abdominal injections was slight. The comparison of k of a given compound from different oily vehicles showed that k was governed predominantly by the distribution coefficient (K) between the oily vehicle and the aqueous subcutaneous medium and depended little on the viscosity of the vehicle. This distributioning relationship was shown through correlation of the rate constants with in vitro distribution coefficients. A plot of log k versus log K for all the compounds tested was linear with a slope of approximately -0.7. This linear relationship allows adequate prediction of absorption rates of other drugs from oily vehicles. The observed subcutaneous absorption rates and behaviors are compared with previous results involving the intramuscular route.

Administration, Topical↗

PubMed1982

Studies on the absorption of practically water-insoluble drugs following injection VI: Subcutaneous absorption from aqueous suspensions in rats.

The absorption characteristics and kinetics of practically water-insoluble drugs following subcutaneous injection of their aqueous suspensions were investigated in intact rats by the local clearance method and compared with those following intramuscular injection reported previously. The plot of the cube root of the residual fraction of the drug in the injection site versus time gave a good linear relationship under various experimental conditions. The absorption rate constant (j) increased with decreasing particle size. This increase was remarkable in the region of mean particle diameter less than 2-3 micrometers, while it was gradual or slight in the region above this. This phenomenon was explained by the fact that the in vivo spreading of particles of more than approximately 3 micrometers was still more limited by the network of the fibrous tissues. Between j and the initial drug concentration (C0) or injection volume (V0), the practically important relationship j alpha C0g V0h (g = -0.66 and h = -0.32) could approximately be derived from the experimental results. Comparison of j values among various compounds with different solubility (C's) in saline but with similar colloidal properties (particle size distribution and sedimentation volume) showed that a log j versus log C's plot gave a nearly straight line with a slope of approximately 0.5. All the results observed for the subcutaneous absorption were similar to those for intramuscular absorption and could reasonably be explained by the kinetic model proposed for intramuscular absorption.

Animals↗

PubMed1988

Characterization of the oral absorption of beta-lactam antibiotics. I. Cephalosporins: determination of intrinsic membrane absorption parameters in the rat intestine in situ.

The oral absorption of five cephalosporin antibiotics, cefaclor, cefadroxil, cefatrizine, cephalexin, and cephradine, has been studied using a single-pass intestinal perfusion technique in rats. Intrinsic membrane absorption parameters, "unbiased" by the presence of an aqueous permeability (diffusion or stagnant layer), have been calculated utilizing a boundary layer mathematical model. The resultant intrinsic membrane absorption parameters are consistent with a significant carrier-mediated, Michaelis-Menten-type kinetic mechanism and a small passive component in the jejunum. Cefaclor colon permeability is low and does not exhibit concentration dependent behavior. The measured carrier parameters (+/- SD) for the jejunal perfusions are as follows: cefaclor, J*max = 21.3 (+/- 4.0), Km = 16.1 (+/- 3.6), P*m = 0, and P*c = 1.32 (+/- 0.07); cefadroxil, J*max = 8.4 (+/- 0.8), Km = 5.9 (+/- 0.8), P*m = 0, and P*c = 1.43 (+/- 0.10); cephalexin, J*max = 9.1 (+/- 1.2), Km = 7.2 (+/- 1.2), P*m = 0, and P*c = 1.30 (+/- 0.10); cefatrizine, J*max = 0.73 (+/- 0.19), Km = 0.58 (+/- 0.17), P*m = 0.17 (+/- 0.03), and P*c = 1.25 (+/- 0.10); and cephradine, J*max = 1.57 (+/- 0.84), Km = 1.48 (+/- 0.75), P*m = 0.25 (+/- 0.07), and P*c = 1.06 (+/- 0.08). The colon absorption parameter for cefaclor is P*m = 0.36 (+/- 0.06, where J*max (mM) is the maximal flux, Km (mM) is the Michaelis constant, P*m is the passive membrane permeability, and P*c is the carrier permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1993

A concise review: iron absorption--the mucin-mobilferrin-integrin pathway. A competitive pathway for metal absorption.

Newly identified iron binding proteins isolated from rat duodenal homogenates permit better understanding of iron absorption. Mucins bind iron at acid pH to keep iron soluble and available for absorption at the more alkaline pH of the duodenum; this explains iron deficiency following prolonged achlorhydria. Integrin (90/150 kD) was identified on the absorptive surface of enterocytes in association with radioiron and is believed to facilitate transit of iron through the microvillous membrane. Mobilferrin, a 56 kD iron binding protein, was isolated from enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrins in the apical cytoplasm. We postulate it accepts dietary iron from integrin and acts as the shuttle protein for iron in the cytoplasm. Since iron in enterocytes remains in equilibrium with body stores, we postulate mucosal iron uptake is regulated by the number of iron binding sites either occupied or unoccupied by iron on mobilferrin. Iron repletion of enterocytes from body stores is accomplished via transferrin receptors on the posterolateral membranes of enterocytes. Increased transfer of iron from blood into absorptive enterocytes occurs in iron replete animals to inhibit mucosal uptake of dietary iron. Little transfer of iron from plasma to enterocytes occurs in iron deficiency. Enhanced mucosal transfer of iron into the body occurs with increased body need for iron. The exact mechanism for mucosal transfer of iron into the plasma has not been defined but may also be mediated by an integrin.

Absorption↗