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At least 127 records · Page 7Linked to original sources

PubMed1989

Intestinal absorption of drugs. I: The influence of taurocholate on the absorption of dantrolene in the small intestine of the rat.

The influence of sodium taurocholate (1) on the intestinal absorption of the lipophilic drug dantrolene (2) was studied in vivo in a chronically isolated internal loop in the rat. Concentrations of 2 were kept below the saturation concentration in saline. Absorption kinetics of 2 were evaluated on the basis of steady-state blood levels, which develop during single-pass perfusions, and on the basis of the rate of disappearance of the drug from the perfusate during recirculating perfusions. Compound 1 at a concentration of 10 mM in the perfusate induced a twofold reduction of the absorption rate compared with the same concentration of 2 in saline. Pretreatment of the absorptive surface with a 10 mM solution of 1 had no detectable effect on the absorption rate of 2 in saline. After perfusions with 10 mM solutions of 1, the perfusate concentration of proteins, phosphorus, and hexoses in the effluent was increased. The reduction of the absorption rate can be ascribed mainly to a reduction of the thermodynamically active concentration of 2 as calculated from the phase-separation model. In addition, 10 mM 1 seems to temporarily increase the barrier function of the mucous layer.

Animals↗

PubMed1979

Linoleic acid absorption in the unanesthetized rat: mechanism of transport and influence of luminal factors on absorption.

Linoleic acid intestinal absorption was studied in the unanesthetized rat. At low (21-1260 micrometer) intraluminal concentrations, absorption took place by facilitated diffusion; while at high (1.26-2.5 mM) concentrations, simple diffusion was the predominant mechanism of transport. At low concentrations (840 micrometer), the equimolar additions of oleic, linolenic, and arachidonic acids or lecithin inhibited the absorption of linoleic acid. Substitution of potassium for sodium in the buffer solution, substitution of Tween 80 for sodium taurocholate, or decrease in the hydrogen ion concentration all resulted in decreased rate of linoleic acid absorption. Increase in sodium taurocholate concentration, or perfusate flow rate increased linoleic acid's absorption. These experiments demonstrate that linoleic acid is absorbed by a concentration-dependent dual mechanism of transport. The absorption rate is modified by the pH, surfactant type and concentration, the simultaneous presence of other polyunsaturated fatty acids, and the thickness of the unstirred water layer.

Animals↗

PubMed1997

Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement.

PURPOSE: It has recently been shown that the absorption enhancing and toxic effects of chitosans are dependent on their chemical composition. In this study, the mechanisms underlying these effects were investigated at the cellular level. METHODS: The effects on epithelial cells of chitosans with different chemical composition, absorption enhancing properties and toxicities were studied in Caco-2 monolayers. Chitosan C( 1:31) has a low degree of acetylation (DA) (1%) and a low m.w. (31 kD), and displays dose-dependent absorption enhancement and cytotoxicity; chitosan C(35:170) has a higher DA (35%) and a higher m.w. (170 kD), is less dose-dependent in absorption enhancement, and is not cytotoxic. A third non-toxic chitosan C(49:22) with a high DA (49%), a low m.w. (22 kD), and no influence on epithelial permeability was used as control. RESULTS: C(1:31) and C(35:170) bound tightly to the epithelium. Cellular uptake of the chitosans was not observed. Both chitosans increased apical but not basolateral cell membrane permeability and induced a redistribution of cytoskeletal F-actin and the tight junction protein ZO-1. This resulted in increased paracellular permeability of hydrophilic marker molecules of different molecular weights. Addition of negatively charged heparin inhibited the cellular and the absorption enhancing effects of the chitosans, indicating that these effects are mediated via their positive charges. The onset of the effects of C(35:170) on apical membrane permeability and tight junction structure was much faster than that of C(1:31). C(49:22) did not influence any of the properties of the Caco-2 cell monolayers studied. CONCLUSIONS: The binding and absorption enhancing effects of chitosans on epithelial cells are mediated through their positive charges. The interaction of chitosans with the cell membrane results in a structural reorganisation of tight junction-associated proteins which is followed by enhanced transport through the paracellular pathway.

Biomarkers↗

PubMed1985

Gastrointestinal absorption as a function of age: xylose absorption in healthy adults.

Xylose oral absorption was examined in 24 healthy male subjects ranging in age from 32 to 85 years. Absorption was evaluated from xylose plasma concentration-time data after administration of a 25 gm po or a 5 gm iv dose. There was no relationship between various estimates of the rate of absorption and age. The absolute oral bioavailability or the extent of xylose absorption showed no relationship to age in our population. In contrast with previous suggestions, xylose absorption does not decline with age. General statements of decreased gastrointestinal absorption efficiency as a function of age may not be correct.

Administration, Oral↗

PubMed1992

Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow--limited percutaneous absorption.

For most drugs delivered by the transdermal route, percutaneous absorption is limited by the rate of release of the drug from the device or by diffusion across the stratum corneum. However, systemic absorption also requires that the drug be taken up by dermal blood vessels. As part of a bioavailability study of a transdermal delivery system, we observed that a concomitant intravenous infusion of nicotine had a marked effect on the absorption kinetics of transdermal nicotine. Plasma concentrations of nicotine rose less rapidly, reached a lower peak, and peaked at a later time, indicating delayed absorption of transdermal nicotine after intravenous nicotine versus after transdermal nicotine administered alone. Nicotine is known to produce cutaneous vasoconstriction. The likely explanation for our observation is that intravenous nicotine constricts dermal blood vessels, thereby limiting percutaneous absorption. Other vasoconstrictor drugs would be expected to retard the absorption of transdermal nicotine and perhaps other transdermal drugs as well.

Administration, Cutaneous↗

PubMed1976

Absorption of galactose by the rat small intestine in vivo: proximal-distal kinetic gradients and a new method to express absorption per enterocyte.

1. The absorption in vivo of D-galactose by the rat small intestine has been examined in proximal jejunum and distal ileum by use of a recirculation-perfusion technique. 2. Multiple sequential perfusions over 4 h produced no subsequent functional or morphological damage in the perfused segments. 3. Absorption of galactose from 8 and 64 mmol/l solutions was found to be independent of flow rate over the range 1-0-6-5 ml/min. 4. Galactose absorption in both the jejunum and the ileum exhibited saturation kinetics of the Michaelis-Menten type, and phlorrhizin sensitivity. Sorbose was only absorbed minimally. These observations demonstrate that galactose is absorbed by carrier-mediated transport and that there is no significant passive diffusive component in vivo. 5. Under the stated experimental conditions, the maximum absorptive capacity was 4-5 times greater in the jejunum than in the ileum. The Michaelis constant for galactose was higher in the jejunum than in the ileum. 6. Enterocytes were isolated from perfused segments and quantified by DNA assay with a correction for yield. In this manner, the absorptive capacity per enterocyte was calculated. 7. The maximum absorptive capacity per enterocyte was 3-5 times greater in the jejunum than in the ileum.

Animals↗

PubMed1978

The measurement of calcium absorption and absorption rate with an external arm radioactivity counter.

1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2. 2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined. 3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administration of 47CaCL2. 4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.

Absorption↗

PubMed1981

A comparison of radioactive calcium absorption tests with net calcium absorption.

1. Four different methods of calculating calcium absorption by radioactive calcium procedures have been compared with each other and with net calcium absorption in calcium-balance studies in 100 consecutive studies on 71 patients. 2. All four isotope procedures yielded highly significant correlations with net calcium absorption derived from the balance studies, but there was little to choose between the validity of the double-isotope and single-isotope procedure judged by these criteria. 3. The rate of calcium absorption calculated from one or other isotope procedure correlated better with net calcium absorption than did the fraction of the radioactive calcium absorbed. 4. The measurement of plasma radioactivity 1 h after single-isotope administration, corrected for body weight, proved almost as useful as the more complex procedures but would be expected to underestimate calcium absorption in states of very high bone turnover.

Calcium↗

PubMed1987

Studies on the effects of dietary zinc dose on 65Zn absorption in vivo and on the effects of Zn status on 65Zn absorption and body loss in young rats.

Weanling male rats were maintained on diets containing 5, 10, 20, 40, 80 or 160 mg zinc/kg for 14 d. On day 15 they received 65Zn either by intraperitoneal injection or in a test meal containing 20 mg Zn/kg. After dosing, the rats were again maintained on the diets they had received previously. Whole-body 65Zn retention was measured immediately after dosing and daily for a further 9 d. From regression analysis of the semi-logarithmic plots of 65Zn retention from 0 to 192 h after 65Zn administration, the true extent of 65Zn absorption and the biological half-life (t1/2) of body 65Zn stores were calculated. At the end of the experiment, the rats were killed and the entire small intestines of some rats from each group were rapidly flushed out to remove food and faecal residues, frozen in liquid nitrogen and stored under an atmosphere of N2 at -20 degrees before separation of cytosolic Zn-binding fractions by gel filtration on Sephadex G-75. The results suggest that rats which received diets that were either deficient (5 mg Zn/kg), marginal (10 mg Zn/kg) or adequate (20-80 mg Zn/kg) in Zn achieved homeostatic regulation of body Zn by changes in both the extent of Zn absorption and excretion. However, when Zn supply was excessive, increasing from 80 to 160 mg Zn/kg, no further changes were seen in Zn absorption, and homeostatic control appeared to be effected entirely by changes in rates of body Zn loss. Gel chromatography of intestinal cytosol on Sephadex G-75 revealed that Zn was associated with two major fractions. The first (peak 1) had a molecular weight (MW) greater than 75 kdaltons and the second (peak 2), a MW of approximately 10 kdaltons and was assumed to be metallothionein. There was no obvious relation between the amount of Zn bound to peak 1 and dietary Zn content. In contrast, the amount of Zn recovered in peak 2 increased linearly with increasing dietary Zn content. Comparisons between the effect of dietary Zn content on Zn bound to peak 2 and 65Zn retention may, depending on the range of Zn intakes, indicate possible roles for intestinal metallothionein in the control of Zn absorption or excretion. A study of the effects of dietary dose of 65Zn on the extent of 65Zn absorption in rats of normal Zn status indicated a possible biphasic relation. At low doses (5-40 mg Zn/kg) 65Zn absorption appeared to exhibit a curvilinear response to increasing 65Zn dose, indicating possibly a saturable process.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2001

Ingestion of insoluble dietary fibre increased zinc and iron absorption and restored growth rate and zinc absorption suppressed by dietary phytate in rats.

We examined the effects of ingestion of five types of insoluble fibre on growth and Zn absorption in rats fed a marginally Zn-deficient diet (6.75 mg (0.103 mmol) Zn/kg diet) with or without added sodium phytate (12.6 mmol/kg diet). The types of insoluble fibre tested were corn husks, watermelon skin, yam-bean root (Pachyrhizus erosus) and pineapple core, and cellulose was used as a control (100 g/kg diet). Body-weight gain in the cellulose groups was suppressed by 57 % by feeding phytate. Body-weight gain in phytate-fed rats was 80 % greater in the watermelon skin fibre and yam-bean root fibre group than that in the cellulose group. Zn absorption ratio in the cellulose groups was lowered by 46 and 70 % in the first (days 7-10) and second (days 16-19) measurement periods with feeding phytate. In the rats fed the phytate-containing diets, Zn absorption ratio in the watermelon skin, yam-bean root and pineapple core fibre groups was 140, 80 and 54 % higher respectively than that in the cellulose group, in the second period. Fe absorption was not suppressed by phytate, however, feeding of these three types of fibre promoted Fe absorption in rats fed phytate-free diets. The concentration of soluble Zn in the caecal contents in the watermelon skin fibre or yam-bean root fibre groups was identical to that in the control group in spite of a higher short-chain fatty acid concentration and lower pH in the caecum. These findings indicate that ingestion of these types of insoluble fibre recovered the growth and Zn absorption suppressed by feeding a high level of phytate, and factors other than caecal fermentation may also be involved in this effect of insoluble fibre.

Animals↗

PubMed1976

Food iron absorption in man II. The effect of EDTA on absorption of dietary non-heme iron.

One hundred and eighty iron absorption tests were performed in 45 normal men to determine the effect of EDTA on the absorption of dietary non-heme iron. The addition of 50 mg EDTA to test meals containing 4.1 mg iron reduced absorption by approximately one-half from meals of both high (standard meal) and low (semisynthetic meal) iron availability. Studies employing dual radioiron labels demonstrated complete isotopic exchange of ferric EDTA with dietary non-heme iron. Further studies were carried out to determine the decrease in food iron absorption at varying levels of EDTA. At a 1:1 molar ratio of EDTA to iron, absorption of non-heme iron was reduced to 72% and at a 2:1 molar ratio, to 50% of absorption without EDTA. These levels of EDTA are within the range believed to be present in the United States diet.

Adolescent↗

PubMed1976

Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorption.

The ability of various animal proteins to enhance the absorption of dietary nonheme iron was evaluated by performing multiple radioiron absorption measurements in 70 volunteer subjects. Protein equivalent substitutions of nine animal foods were made in two basic test meals. The first was a standard meal of high iron availability (mean absorption, 8.3%) containing beef muscle as the animal protein. The second was a semisynthetic meal of low iron availability (mean absorption, 1.4%) containing ovalbumin as the protein source. Two categories of animal protein were defined. Substitution of beef, lamb, pork, liver, fish, and chicken for the egg ovalbumin in the sannisynthetic meal resulted in a significant, 2-fold to 4-fold increase in iron absorption whereas no increase was observed with milk, cheese, or egg. Reciprocal findings were obtained when these foods were substituted for the beef contained in the standard meal. All sources of animal proteins are not equivalent in their effect on nonheme iron absorption.

Absorption↗

PubMed1983

Comparative lymphatic absorption of sitosterol, stigmasterol, and fucosterol and differential inhibition of cholesterol absorption.

Studies have been conducted on the lymphatic absorption of sitosterol (24 alpha-ethyl cholesterol), stigmasterol (delta 22, 24 alpha-ethyl cholesterol), and fucosterol (24-ethylidine cholesterol) when administered intragastrically to rats. In addition, the effect of each sterol on absorption of endogenous cholesterol has been assessed by including tracer cholesterol in the administered test emulsion. Analysis of 24-h lymph collections by GLC-mass spectrometry demonstrated that all three sterols were poorly absorbed to the extent of only 3 to 4% of the administered dose of 50 mg. In contrast, cholesterol absorption under similar conditions was about 42% of the administered dose. Administration of either sitosterol or stigmasterol resulted in an equally effective inhibition of cholesterol absorption (54%). Under identical conditions fucosterol had no effect on absorption of luminal cholesterol. The data suggest that the mechanism(s) for intestinal discrimination of sterols for absorption may be independent of the mechanism for interference with efficient cholesterol uptake by the intestine.

Absorption↗

PubMed1991

Absorption of low and therapeutic doses of ferric maltol, a novel ferric iron compound, in iron deficient subjects using a single dose iron absorption test.

Ferric maltol is a novel ferric iron compound with potential use as an oral therapy for iron deficiency anaemia. Using a single, low dose iron absorption test we compared absorption of ferric maltol with absorption of ferrous sulphate in 21 iron deficient subjects. Absorption of 10 mg of ferric maltol as either aqueous solution or a single tablet compared favourably with that of an equivalent dose of ferrous sulphate. At a higher, more therapeutic dose of 60 mg elemental iron as tablets, absorption of ferric maltol appeared to be both more rapid and total absorption greater, than that seen with ferrous sulphate. We conclude that iron from ferric maltol, both at low dose and higher, more therapeutic doses, is at least as well absorbed as from ferrous sulphate. Ferric maltol is the first ferric iron formulation to be absorbed to a degree equivalent to that of ferrous iron salts and may represent a viable form of administration for ferric iron in the treatment of iron deficiency anaemia.

Adult↗

PubMed1989

The Journal of clinical Investigation, Volume 41, 1962: iron absorption. IV. The absorption of hemoglobin iron.

The absorption of radioiron in rabbit hemoglobin, hemin, and ferritin has been compared to that of ferrous salt in healthy volunteers and in subjects with iron-deficiency anemia. At a dosage level of 5 mg elemental iron, hemoglobin iron was as well or better absorbed than ferrous salts in the normal subject. Absorption of hemoglobin iron increased less, however, in the iron-depleted or iron-deficient subject. In contrast to the absorption of ferrous salts, that of hemoglobin iron was not decreased by food or by phytate nor increased by ascorbic acid. The absorption of hemin iron was also not decreased by food. Iron absorbed from hemoglobin appeared in the plasma later than that from ferrous salts, but was found to be similarly dialyzable at acid pH with EDTA. These findings suggest that iron in heme complexes is absorbed as a porphyrin complex without conversion to the free ionized form. It is further apparent that there is less effective mucosal regulation of absorption of iron in this form. Finally, the present hypothesis of iron absorption based on the behavior of iron salts is not adequate for all types of food iron.

Absorption↗

PubMed1976

Alcohol and absorption from the small intestine. 1. Impairment of absorption from the small intestine in alcoholics.

An absorption screen was performed in 10 chronic alcoholic patients within a few days of admission due to an acute alcoholic episode. Impaired absorption of d-Xylose was noted in three patients and low leucocyte ascorbic acid and serum folate levels in five. No abnormality was detected in jejunal histology. The absorption of water and electrolytes from the jejunum was studied in these patients using a triple-lumen tube perfusion system. The mean rate of absorption of water in the alcoholic subjects (50-0 +/- 2-3 ml/h) was significantly lower (P less than 0-001) than the mean value in 14 healthy control subjects (205 +/- 15-9 ml/h). A significant reduction of Na+ and Cl-absorption was also demonstrated in the alcoholic subjects. These results indicate that patients with acute-on-chronic alcoholism may have a function impairment of water and electrolyte absorption from the jejunum. This may, in part, account for some of the nutritional deficiencies in such patients and for symptoms such as diarrhoea which may be present.

Adult↗

PubMed1987

Studies on drug absorption from oral cavity. II. Influence of the unstirred water layer on absorption from hamster cheek pouch in vitro and in vivo.

The influence of the unstirred water layer (UWL) adjacent to the membrane surface of the hamster cheek pouch on absorption was studied in vitro and in vivo. The tissue uptake rate of 14C-laurylalcohol was determined in vitro and the value of the effective resistance of UWL (RW) was calculated. RW values were reduced by increasing the stirring rate of the mucosal solution. In vitro permeation of 14C-benzoic acid into the serosal compartment was also increased in the well-stirred condition. Thus, the existence of UWL as an effective diffusion barrier for drug absorption from the hamster cheek pouch was suggested. To clarify the influence of the existence of UWL on the absorption in vivo, the apparatus for luminal stirring was newly devised. When the luminal solution was well-stirred, the absorption of benzoic acid in the lower pH region significantly increased, resulting in the disappearance of the shift of pH-absorption curve for benzoic acid. Furthermore, the luminal stirring increased the absorption rate constant for salicylic acid. From these experimental results, it is suggested that UWL plays a part of barriers against drug permeation in the hamster cheek pouch.

Administration, Buccal↗

PubMed1986

Studies on drug absorption from oral cavity: physicochemical factors affecting absorption from hamster cheek pouch.

A new experimental method using a hamster cheek pouch in vivo for studying absorption processes across the keratinized oral mucous membrane was developed and some characteristics of the oral-mucosal absorption were clarified. A positive correlation between the absorption rate and the lipophilicity was observed in 18 aromatic compounds examined. The absorption of ionizable compounds was poor in the ionized form. These results suggest that the absorption from the keratinized hamster cheek pouch is due to a passive diffusion mechanism and obeys pH-partition hypothesis. The systemic transfer of salicylic acid after intra-cheek-pouch administration could be approximated by the first-order absorption model including a lag time process and the plasma levels found were consistent with this model.

Absorption↗