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At least 109 records · Page 6Linked to original sources

PubMed1998

Oral absorption tests: absorption site of each substrate.

Three oral absorption tests have been used in patients with short bowel syndrome (SBS) to evaluate the absorption site of each substrate. In this study, three absorption tests were applied: the oral pancreatic function test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA), the D-xylose tolerance test, and the oral fat tolerance test. Examinations were performed in eight patients with either a duodenostomy or a jejunostomy located less than 60 cm from the ligament of Treitz, and in a patient with an end ileostomy. Forty-six healthy volunteers participated as controls for the oral fat tolerance test. PABA and D-xylose concentrations were measured in urine. The serum triacylglycerol concentration was determined at 0, 1, 2, and 3 h after ingestion. All eight patients with SBS demonstrated pathologic absorption on each test. We conclude that small bowel integrity is critical for evaluation of the NBT-PABA test. We also determined that the duodenum and proximal jejunum do not play an important role in the absorption of D-xylose and triacylglycerol. We could also evaluate limitations and advantages of the other kinds of oral absorption tests and nutrients through patients with SBS.

4-Aminobenzoic Acid↗

PubMed1990

Absorption of polyethylene glycols 600 through 2000: the molecular weight dependence of gastrointestinal and nasal absorption.

Polyethylene glycols (PEGs) 600, 1000, and 2000 were used to study the molecular weight permeability dependence in the rat nasal and gastrointestinal mucosa. Absorption of the PEGs was measured by following their urinary excretion over a 6-hr collection period. HPLC methods were used to separate and quantitate the individual oligomeric species present in the PEG samples. The permeabilities of both the gastrointestinal and the nasal mucosae exhibited similar molecular weight dependencies. The steepest absorption dependence for both mucosae occurs with the oligomers of PEG 600, where the extent of absorption decreases from approximately 60% to near 30% over a molecular weight range of less than 300 daltons. Differences in the absorption characteristics between the two sites appear in the molecular weight range spanned by PEG 1000. For these oligomers, the mean absorption from the nasal cavity is approximately 14%, while that from the gastrointestinal tract is only 9%. For PEG 2000, mean absorption decreases to 4% following intranasal application and below 2% following gastrointestinal administration. Within the PEG 1000 and 2000 samples, however, very little molecular weight dependency is seen among the oligomers. In the range studied, a distinct molecular weight cutoff was not apparent at either site.

Absorption↗

PubMed1985

Studies on the absorption of sodium guaiazulene-3-sulfonate. II. Absorption mechanism from nasal and intestinal membrane.

To examine the absorption mechanism of sodium guaiazulene-3-sulfonate (GAS) through the nasal and the intestinal membrane, the apparent absorption rate under the various experimental conditions was measured with the in situ perfusion method in rats, and the apparent partition coefficient of GAS was also determined. The absorption rate of GAS changed biphasically depending on the initial GAS concentration in the perfusate. At the lower concentration range (less than 1 mg/ml), the absorption rate of GAS decreased with the increased in the concentration, and the absorption was inhibited by HgCl2 and ouabain. However, at the higher concentration range (greater than 1 mg/ml), the absorption rate from the nasal mucosa increased markedly with the increase in the concentration, and ouabain had no effect. The apparent partition coefficient of GAS increased with the increase in the concentration of GAS, and GAS was found to be readily transferred to the organic phase by forming ion-pair complexes with the cation such as NH4+ ion. These results suggested that GAS is absorbed through the nasal membrane by at least two kinds of mechanisms: one is a carrier mediated system and the other is a hydrophobic interaction with the nasal mucosa which is increased by forming an ion-pair complex of GAS with cation.

Absorption↗

PubMed1985

[Comparative studies on the enzymatic absorption of protein hydrolysates in the small intestine of the rat. 3. The absorption trypsins thermatatic and trypsin-thermatatic hydrolysates of a fava bean protein isolate compared to an equimolar mixture of free amino acids].

Tryptic, thermitatic, and tryptic-thermitatic Faba bean protein hydrolyzates as well as their equimolar mixture of amino acids were perfused through proximal and distal parts of the intestine (10 cm length) of non-narcotized rats. The total amino-acid concentration of the perfused solution was 50 mM. The absorption of nitrogen and total amino acids from the tryptic and tryptic-thermitatic hydrolyzates was lower than that from the amino-acid mixture, the absorption from the thermitatic hydrolyzate was in accordance with that from the amino-acid mixture. The absorption pattern of the amino acids which preferably undergo a peptidic absorption is similar with the three hydrolyzates: in the proximal intestinal part this concerns glutamic acid and serine, in the distal intestinal part--methionine, alanine, glycin, and serine. The absorption pattern of the amino acids is different between the three hydrolyzates and the amino-acid mixture. Between the absorption pattern of the amino acids from the three hydrolyzates little differences were evident only in the proximal intestinal part. The coefficients of variation of the tryptic-thermitatic hydrolyzates are in accordance with those of the amino-acid mixture, whereas that of the thermitatic hydrolyzates is significantly lower. In the distal intestinal part all supplied forms are more rapidly absorbed than in the proximal part of the intestine.

Amino Acids↗

PubMed1985

[Comparative study of the absorption of enzymatic protein hydrolysates in the small intestine of the rat. 2. The absorption of tryptic, thermitatic and tryptic-thermitatic casein hydrolysates compared with the equimolar composition of free amino acids].

Tryptic, thermitatic, and tryptic-thermitatic casein hydrolyzates as well as their equimolar amino-acid mixture were perfused through proximal and distal parts of the intestine (10 cm length) of nonanaesthesized rats. The total amino-acid concentration of the perfused solution was 50 mM. The absorption of nitrogen and total amino acids respectively did not reveal significant absorption advantages in favour of the hydrolyzates. In contrast to this, some peptidic bound amino acids of these hydrolyzates show a significantly better absorption as compared to free amino acids. At this, dependences of the kind of hydrolyzate and the part of the intestine are evident. Glutamic acid, e.g. is generally more rapidly absorbed when peptidic bound; methionine is more rapidly absorbed only from the thermitatic and tryptic-thermitatic hydrolyzates, and alanine and glycin only in the distal part of the intestine. Independent of the amino acid or peptide substrate the total absorption of all the amino acids is higher in the distal part of the intestine. The comparison concerning the ranking order of the single amino-acid absorption rates shows in the two parts of the intestine distinct differences between the amino-acid mixtures and the enzymatic hydrolyzates. The lowest differences were found between the thermitatic and the tryptic-thermitatic hydrolyzate. Both of them have approximately the same degrees of hydrolysis (30 and 35%, respectively). The variability of the amino-acid absorption from the three casein hydrolyzates is lower in comparison with the amino-acid mixture. The tryptic-thermitatic hydrolyzates have the lowest coefficients of variability.

Amino Acids↗

PubMed1978

GI absorption of beta-lactam antibiotics I: kinetic assessment of competing absorption and degradation in GI tract.

An equation was derived for the simultaneous assessment of rate constatns for absorption and nonenzymatic degradation of unstable drugs in in situ absorption experiments. The equation was substantiated by using a variety of beta-lactam antibiotics in the recirculation technique through the rat small intestine. Plots of the apparent first-order rate constant for the disappearance of the drug from the gut lumen versus the reciprocal of the volume of recirculating solution yielded a straight line with a slope equal to the intrinsic absorption rate constant and with an intercept equal to the nonenzymatic degradation rate constant in the GI lumen. The kinetic method for evaluation of the absorption rate constant also was developed for a more complex situation in the GI lumen involving absorption, nonenzymatic degradation, and enzymatic metabolism. The proposed method was confirmed with carbenicillin indanyl, which was metabolized rapidly to carbenicillin by the action of nonspecific esterase in the intestine. In the absence of information of Michaelis--Menten kinetic parameters, the present method is advantageous for evaluation of the intrinsic absorption rate of all unstable drugs.

Animals↗

PubMed1982

Carbenicillin prodrugs: kinetics of intestinal absorption competing degradation of the alpha-esters of carbenicillin and prediction of prodrug absorbability from quantitative structure-absorption rate relationship.

The intestinal absorption of alpha-esters of carbenicillin disodium, carbenicillin phenyl sodium, and carbenicillin indanyl sodium was investigated using the in situ rat intestinal recirculating method. In the in situ intestinal lumen at pH 7, two prodrugs were rapidly converted to poorly absorbable carbenicillin, possibly by the action of intestinal nonspecific esterase in competition with the slow absorption of prodrugs. At pH 5, the reduced action of esterase and the increased absorption rate after 3 hr resulted in 50 and 60% absorption of carbenicillin phenyl sodium and carbenicillin indanyl sodium, respectively. The absorption rate constants determined for both prodrugs were in good agreement with the prediction from the quantitative structure-absorption rate relationship derived from the two-compartment aqueous diffusion model.

Animals↗

PubMed1983

Vaginal absorption of a potent luteinizing hormone-releasing hormone analogue (leuprolide) in rats II: mechanism of absorption enhancement with organic acids.

Organic acids such as citric acid enhance the vaginal absorption of luteinizing hormone-releasing hormone, the potent analogue (leuprolide), and insulin. The mechanism of this absorption enhancement was investigated with leuprolide and hydrophilic markers such as phenol red and Evan's blue. The absorption of the analogue was increased by lowering the pH of the solution and increased more by adding citric, succinic, tartaric, and malonic acids. The absolute bioavailability after vaginal administration of the 5% citric acid solution was 16.7% at pH 3.5 and 38.4% at pH 1.8. The enhancing potency of the absorption correlated well with the chelating ability of the organic acids. The vaginal absorption of phenol red was also enhanced with citric acid and edetic acid, but the enhancing effect of edetic acid was eliminated by adding equimolar calcium ion. These results suggest that the acidifying and chelating abilities of the acids may result in a potent enhancement of the vaginal absorption of leuprolide. A leakage experiment using Evan's blue on the vaginal membrane indicated that the blood-vaginal epithelium barrier was loosened with the administration of citric acid; this change was overcome rapidly.

Absorption↗

PubMed1983

Involvement of active sodium transport in the rectal absorption of gentamicin sulfate in the presence and absence of absorption-promoting adjuvants.

The involvement of active sodium transport in the rectal absorption of gentamicin sulfate was examined in rats, employing aqueous microenemas of known total ionic strength (mu) in the presence or absence of absorption-promoting adjuvants. Rectal gentamicin bio-availability, which is negligible (1 +/- 1.2%) at an ionic strength of 0.15 without adjuvants, is significantly (p less than 0.01) increased by including adjuvants in the formulation (sodium salicylate, 12 +/- 4.0%; sodium-5-bromosalicylate, 59 +/- 15.1%; disodium ethylene (dinitrilo)tetraacetate, 24 +/- 9.3%). Pretreating the rectal mucosa cells with ouabain, a specific inhibitor of active sodium transport, significantly (p less than 0.01) reduced gentamicin absorption in response to all three adjuvants. In contrast to previous findings with sodium chloride, high ionic strength choline chloride (mu = 1.056) did not promote gentamicin absorption. The data indicate that active sodium transport is an integral component of rectal absorption of water-soluble compounds and may be involved in the mechanism of action of absorption-promoting adjuvants.

Adjuvants, Pharmaceutic↗

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↗