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At least 199 records · Page 11Linked to original sources

PubMed1987

Effects of dose, pH, and osmolarity on nasal absorption of secretin in rats. II: Histological aspects of the nasal mucosa in relation to the absorption variation due to the effects of pH and osmolarity.

Nasal absorption of secretin in rats was enhanced in an acid solution, and the maximum absorption was observed at a sodium chloride solution molarity of 0.462. In order to examine reasons for the variation of absorbability caused by the change of pH and osmolarity in secretin preparations, both a pretreatment study, in which the nasal mucosa was treated with placebo prior to the administration of a secretin preparation, and a histological study were conducted in rats. The nasal absorption of secretin was determined by measuring the increased secretin of pancreatic juice. Similar profiles of nasal absorption, both after intranasal administration of secretin preparations and as a result of pretreatment effects, were obtained in studies of the effects of pH and osmolarity. However, in the pH-effect study, the absorption with the use of active preparations was observed to be significantly larger than that with the pretreatment effect below a pH of 4.79, and significantly smaller than that with the pretreatment effect at a pH of 7 to 8. The results of histological studies revealed structural changes of the epithelial cells of the nasal mucosa at pH 2.94, and shrinkage of epithelial cells was observed at a sodium chloride solution molarity of 0.462.

Absorption↗

PubMed2006

Plasma holotranscobalamin compared with plasma cobalamins for assessment of vitamin B12 absorption; optimisation of a non-radioactive vitamin B12 absorption test (CobaSorb).

BACKGROUND: A recently developed non-radioactive vitamin B(12) absorption test (CobaSorb) was further explored to identify the best marker for reflection of vitamin B(12) absorption and to determine the duration of the test. METHODS: Seventy-eight healthy individuals (age 21-81 years) were given three oral doses of 9 microg vitamin B(12) per day for 5 successive days. Non-fasting blood samples were collected on days 1 to 5 before administration of vitamin B(12) and on day 8. Cobalamins and holotranscobalamin were measured. RESULTS: Performance of the vitamin B(12) absorption test was evaluated in individuals with holotranscobalamin or cobalamins below the 75% percentiles. We used a change greater than 2xCV(day-to-day) in holotranscobalamin (22%) and cobalamins (12%) to indicate a change caused by absorption of vitamin B(12). Among individuals with a baseline holotranscobalamin below the 75% percentile (<75 pmol/L, n=57), 98% had an increase in holotranscobalamin >22% from day 1 to day 3. In contrast, only 72% of the individuals with baseline cobalamins below the 75% percentile (<335 pmol/L, n=57) had an increase in cobalamins >12%. CONCLUSIONS: In healthy individuals with baseline holotranscobalamin <75 pmol/L, vitamin B(12) absorption is well reflected by an increase in holotranscobalamin after 2 days administration of oral vitamin B(12).

Adult↗

PubMed2005

The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations.

The aim of this study was to compare the oral absorption of two weak bases including their pH-independent controlled-release preparations using an in vitro evaluation system. This system is able to simulate dissolution of drugs, pH change and permeation of drugs through the epithelial cell membrane in the gastrointestinal tract. Albendazole-polymers solid dispersion and pH-independent sustained-release granules of dipyridamole were prepared by using a solvent method. Elution profiles and predicted absorption of these preparations in gastric pH conditions similar to those in healthy subjects and patients with achlorhydria were compared with those of a physical mixture and commercial tablets. When a physical mixture or commercial tablets were used, the elution profile and predicted absorption of both albendazole and dipyridamole were extremely pH-dependent. On the other hand, when a solid dispersion and granules were used, elution and predicted absorption were not affected by changes in pH of the flowing solution in a drug-dissolving vessel. These results are in agreement with the results of our previous in vivo study using gastric acidity-controlled rabbits. Our results suggest that this in vitro system is useful for the evaluation of oral absorption of pH-independent controlled-release preparations.

Achlorhydria↗

PubMed2005

Effects of absorption promoters on insulin absorption through colon-targeted delivery.

The aim of this study were to investigate the effect of sodium glycocholate (GC-Na) as an absorption promoter and the effects of the co-administration of GC-Na and various absorption promoters on orally administered insulin absorption utilizing a colon-targeted delivery system. The system containing insulin and GC-Na (CDS) was administered to dogs, and plasma glucose and insulin levels were then measured at 24h after administration. For CDS, the C(max) in plasma glucose level was significantly higher than a reference formulation without GC-Na. The pharmacological availability for CDS was not significantly higher than the reference formulation. In contrast, CDS with poly(ethylene oxide) as a gelling agent (CDSP) showed prolonged hypoglycemia effects. The pharmacological availability was 5.5% and significantly different from the reference formulation. The absolute bioavailability for CDS was 0.25%, and for CDSP it was 0.42%. Consequently, the results of this study demonstrated that colon-specific delivery of insulin with GC-Na was more effective in increasing hypoglycemic effects after oral administration, and the combination of GC-Na and poly(ethylene oxide) tended to prolong the colonic absorption of insulin and might be more effective for improvement of orally administered insulin absorption utilizing the colon-targeted delivery system.

Administration, Oral↗

PubMed1999

Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase knockout mice.

Carboxyl ester lipase (CEL; EC 3.1.1.13) hydrolyzes cholesteryl esters and retinyl esters in vitro. In vivo, pancreatic CEL is thought to liberate cholesterol and retinol from their esters prior to absorption in the intestine. CEL is also a major lipase in the breast milk of many mammals, including humans and mice, and is thought to participate in the processing of triglycerides to provide energy for growth and development while the pancreas of the neonate matures. Other suggested roles for CEL include the direct facilitation of the intestinal absorption of free cholesterol and the modification of plasma lipoproteins. Mice with different CEL genotypes [wild type (WT), knockout (CELKO), heterozygote] were generated to study the functions of CEL in a physiological system. Mice grew and developed normally, independent of the CEL genotype of the pup or nursing mother. Consistent with this was the normal absorption of triglyceride in CELKO mice. The absorption of free cholesterol was also not significantly different between CELKO (87 +/- 26%, mean +/- SD) and WT littermates (76 +/- 10%). Compared to WT mice, however, CELKO mice absorbed only about 50% of the cholesterol provided as cholesteryl ester (CE). There was no evidence for the direct intestinal uptake of CE or for intestinal bacterial enzymes that hydrolyze it, suggesting that another enzyme besides CEL can hydrolyze dietary CE in mice. Surprisingly, CELKO and WT mice absorbed similar amounts of retinol provided as retinyl ester (RE). RE hydrolysis, however, was required for absorption, implying that CEL was not the responsible enzyme. The changes in plasma lipid and lipoprotein levels to diets with increasing lipid content were similar in mice of all three CEL genotypes. Overall, the data indicate that in the mouse, other enzymes besides CEL participate in the hydrolysis of dietary cholesteryl esters, retinyl esters, and triglycerides.

Animals↗

PubMed1990

Solute absorption from the airways of the isolated rat lung. II. Effect of surfactants on absorption of fluorescein.

To determine the effects on the pulmonary barrier of several surface active agents, a series of metered dose inhalers (MDIs) was prepared and used to dose aerosolized surfactant to the airways of isolated perfused rat lungs. The MDIs contained a range of concentrations, from 0.1 to 5.0% (w/w), of either oleic acid, oleyl alcohol, or Span 85, which released approximately 45 micrograms (0.1%, w/w) to approximately 1660 micrograms (5.0%, w/w) of surfactant per actuation. The permeability of the pulmonary barrier was assessed by the rate of transfer of disodium fluorescein dosed as 100 microliters of aqueous solution (1 mg/ml) after administering the surfactants. Some 12.1 +/- 4.7% of the recovered surfactant, per dose, was assessed to reach the pulmonary regions of the lung. All surfactants tested caused an increase in fluorescein transfer rates. A single actuation from the MDI containing 5% (w/w) oleic acid produced gross edema in all lungs tested within 40 min and the first-order half-lives of absorption were reduced almost threefold, from 12.9 +/- 2.5 min for controls to 4.5 +/- 0.8 min. Differences in absorption were noted between the acid and the alcohol, which is consistent with the hypothesis that both the hydrocarbon chain and the polar head group have roles in the altered permeability to fluorescein. The absorption of fluorescein when dosed from the MDI containing 5% (w/w) Span 85 was increased but all surfactants dosed from the lowest concentration MDI of 0.1% (w/w) did not alter absorption rates of the dye relative to those of controls. Results are discussed in light of current interest in absorption enhancement and the presence of surfactants in currently marked MDIs.

Absorption↗

PubMed1990

Bile salt-fatty acid mixed micelles as nasal absorption promoters of peptides. II. In vivo nasal absorption of insulin in rats and effects of mixed micelles on the morphological integrity of the nasal mucosa.

The effectiveness of mixed micelles in promoting nasal absorption of peptides has been demonstrated in vivo by employing insulin as a model compound. Insulin in the absence of adjuvants was not absorbed following intranasal administration. The results confirmed previous findings by others that absorption of insulin via alternative routes required absorption enhancers. Mixed micelles between NaGC and linoleic acid were found to rapidly deliver insulin into systemic circulation, with a concomitant decrease in plasma glucose. The extent of the hypoglycemic response was significantly greater than that produced by NaGC alone (55 vs 47%, P less than 0.05). Emulsion of linoleic acid, on the other hand, did not produce any significant insulin absorption. The findings thus supported previous in situ data that mixed micelles were more effective than NaGC or linoleic acid in promoting nasal absorption of peptides. Histopathologic examination of the rat nasal mucosa revealed that the extent of morphological alterations caused by mixed micelles was of mild to moderate severity even after 5 hr of exposure. However, studies involving more frequent and prolonged exposures are necessary to assess the practicality of these adjuvants before any clinical application can be attempted.

Absorption↗

PubMed1996

Transport of drugs across the Xenopus pulmonary membrane and their absorption enhancement by various absorption enhancers.

PURPOSE: The permeability of drugs across the Xenopus pulmonary membrane and the effects of various absorption enhancers on their absorption were examined using an in vitro Ussing chamber technique. METHODS: Phenol red and fluorescein isothiocyanate-labeled dextrans (FDs) with different molecular weights were chosen as water-soluble model drugs. Absorption enhancers used in this study were N-lauryl-beta-D-maltopyranoside (LM), linoleic acid-HC060 mixed micelle (MM), sodium glycocholate (Na-GC), sodium caprate (Na-Cap), sodium salicylate (Na-Sal) and disodium EDTA (EDTA). RESULTS: The permeability of drugs gradually decreased with increasing their molecular weights, and the absorption of phenol red significantly increased by these absorption enhancers. Among these additives, LM, MM and Na-Cap appeared to be more effective for enhancing the permeability of drugs than the others. Furthermore, we plotted the logarithm of apparent permeability coefficient (Papp) of these drugs against the logarithm of their molecular weights. There exists a good correlation between these parameters. We measured transmembrane resistance(Rm) of Xenopus pulmonary membrane during the transport experiment to examine the membrane integrity. The average Rm value was about 700 omega.cm2, and this value was maintained for 3 hr. CONCLUSIONS: This method is useful for estimating the transport characteristics of drugs across the pulmonary membrane.

Absorption↗

PubMed1992

Pharmacokinetic analysis of drug absorption from muscle based on a physiological diffusion model: effect of molecular size on absorption.

In a rabbit hind leg perfusion experiment, the absorption of radiolabeled water and carbohydrates of various molecular sizes from muscle was analyzed using a physiological diffusion model and, also, by statistical moment analysis. The model takes into account diffusion in the interstitial space, transcapillary movement, and removal by the blood circulation and pharmacokinetic parameters representing these processes were computed by curve-fitting. The apparent diffusion coefficients of water and small sugars in the interstitial space (Dm) were proportional to their free diffusion coefficients in water (Df), whereas the diffusion of 14C-inulin was hampered by interstitial structures. The first moments of each absorption process were also determined to assess the quantitative contribution of each absorption process to overall absorption. For carbohydrate molecules, residence time in the depot (td) accounted for most of the absorption time after injection, whereas for 3H-water, residence times in muscle (tm) and in the depot (td) were similar.

Absorption↗

PubMed1994

Solute absorption from the airways of the isolated rat lung. IV. Mechanisms of absorption of fluorophore-labeled poly-alpha,beta-[N(2-hydroxyethyl)-DL-aspartamide].

The pulmonary absorption kinetics of a single molecular weight distribution (MWD) of fluorophore-labeled poly-alpha,beta-[N(2-hydroxyethyl)-DL-aspartamide] (F-PHEA), a hydrophilic and biocompatible synthetic polypeptide, were studied in the isolated, perfused rat lung (iprl) as functions of administered polymer concentration, dose, vehicle, and presence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecular weights (Mw and Mn, respectively) using high-performance gel-permeation chromatography. Values for Mw and Mn were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polymer concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, Vmax, of approximately 180 micrograms or 0.027 mumol/hr. Coadministration of fluorophore-free PHEA was capable of depressing the absorption of F-PHEA. The transport process for F-PHEA appeared to have a molecular weight limit of about 7 kD for this hydrophilic polymer.

Absorption↗

PubMed1984

Oxalate absorption and postprandial urine supersaturation in an experimental human model of absorptive hypercalciuria.

The effect of 1.25-dihydroxyvitamin D [1,25-(OH)2D] on dietary oxalate absorption and postprandial urine supersaturation with calcium oxalate was determined in 11 normal subjects. 1,25-(OH)2D increased the urinary excretion of orally administered [14C]oxalate in the 8 h period after a liquid meal containing 1.875 mmol of calcium and 0.83 mmol of oxalate (P less than 0.01), and during a 48 h period when the subjects ingested a diet containing 25 mmol of calcium and 3.3 mmol of oxalate/day (P less than 0.01); however, 1,25-(OH)2D administration had no effect on [14C]oxalate excretion when calcium was removed from the liquid meal. 1.25-(OH)2D increased 24 h urinary oxalate excretion from 28.7 +/- 2.1 mmol/mol of creatinine to 36.8 +/- 2.6 mmol/mol of creatinine (P less than 0.05) on the 10 mmol/day calcium diet and from 26.4 +/- 2.9 to 33.2 +/- 2.2 mmol/mol of creatinine (P less than 0.1) on the 25 mmol/day calcium diet. A linear correlation (r = 0.72) was found between plasma 1,25-(OH)2D levels and urinary [14C]oxalate excretion after the liquid meal. 1,25-(OH)2D administration produced postprandial supersaturation of urine with calcium oxalate and calcium oxalate crystalluria. These studies suggest that 1,25-(OH)2D increases oxalate absorption (and urinary excretion) by increasing calcium absorption, which results in less binding of calcium to oxalate in the intestine; therefore more oxalate is available for absorption. The combined effect of increased calcium and oxalate absorption results in postprandial supersaturation of urine with calcium oxalate, with resultant crystalluria.

Adult↗

PubMed1979

The measurement of food iron absorption in man. A methodological study on the measurement of dietary non-haem-Fe absorption when the subjects have a free choice of food items.

1. The present study was considered as a first step to develop a method to measure food iron absorption from realistic common meals prepared and consumed by the subjects themselves in their own homes. The absorption of Fe from the meals was measured by means of the extrinsic-tag method modified to allow for a free choice of food items. 2. The mean Fe intake was 2.79 mg and the mean Fe absorption approximately 0.30 mg. The Fe status of the subjects corresponded to 31.5% absorption from a reference dose solution containing 3 mg elemental Fe as ferrous ascorbate. The variation in food Fe absorption obtained in this field study was found to be of the same magnitude as that obtained in studies performed under more controlled conditions as in the laboratory. 3. The conclusion was drawn that the proposed method could be used in realistic field studies aimed at, for example, explaining or preventing a high prevalence of deficiency. A suffciently long run-in period and a careful instruction of the subjects was considered essential for the design of future field studies.

Adult↗

PubMed2006

Total zinc absorption in young women, but not fractional zinc absorption, differs between vegetarian and meat-based diets with equal phytic acid content.

Zn bioavailability is often lower in vegetarian diets mainly due to low Zn and high phytic acid contents. The objective of the present study was to determine the fractional and total absorption of Zn from a vegetarian diet in comparison with meat diets with equal concentrations of phytic acid. A randomized cross-over design, comprising three whole-day diet periods of 5 d each, with a vegetarian diet or diets containing Polish-produced meat or Danish-produced meat, was conducted. Twelve healthy female subjects completed the study. All diets had a high content of phytic acid (1250 micromol/d) and in the meat diets the main meals contained 60 g pork meat. All main meals were extrinsically labelled with the radioactive isotope 65Zn and absorption of Zn was measured in a whole-body counter. The mean Zn content of the whole-day diet was: Polish meat diet 9.9 (SE 0.14) mg, Danish meat diet 9.4 (SE 0.19) mg and vegetarian diet 7.5 (SE 0.18) mg. No difference was observed in the fractional absorption of Zn (Polish meat diet: 27 (SE 1.2) %, Danish meat diet: 27 (SE 1.9) % and vegetarian diet: 23 (SE 2.6) %). A significantly lower amount of total Zn was absorbed from the vegetarian diet (mean Zn absorption of Polish meat diet: 2.7 (SE 0.12) mg/d (P<0.001), Danish meat diet: 2.6 (SE 0.17) mg/d (P=0.006) and vegetarian diet: 1.8 (SE 0.20) mg/d). In conclusion, the vegetarian diet compared with the meat-based diets resulted in lower amounts of absorbed Zn due to a higher content of Zn in the meat diets, but no difference was observed in the fractional absorption of Zn.

Adult↗

PubMed1986

[Nitrogen and amino acid absorption in the small intestine of growing pigs. 2. Apparent and true crude protein digestibility and amino acid absorption to the end of the small intestine].

Studies of the apparent and true ileal digestibility of crude protein and the apparent and true amino acid (AA) absorption were carried out with 7 female pigs in the live weight range between 22 and 34 kg after ileorectostomy. Protein sources of varied quality with regard to the method of treatment (toasted) and untoasted soybean oilmeal) and to the AA composition (vital gluten or vital gluten + L-lysine X HCl) were used. Distinct differences regarding the apparent ileal digestibility of crude protein and the apparent absorption of amino acids were discovered between the protein sources, the cause of which is to be seen in the different amounts of endogenous N. The true ileal digestibility of crude protein and amino acid absorption were partly distinctly higher than the values of the apparent ileal digestibility of crude protein and AA absorption. On the whole one can say that the results of the investigation gained by means of ileorectostomy can be compared to the values gained from cannulated animals. Thus the experimental method used is suitable for studying the absorption process to the end of the small intestine of pigs.

Amino Acids↗

PubMed1987

Nasal and conjunctival contributions to the systemic absorption of topical timolol in the pigmented rabbit: implications in the design of strategies to maximize the ratio of ocular to systemic absorption.

The primary purpose of this study was to determine the relative contribution of the nasal and the conjunctival mucosae to the systemic absorption of topically applied timolol in the pigmented rabbit. The nasal mucosa was found to be about 2.5 times more efficient than the conjunctival mucosa in contributing to systemic timolol absorption, which occurred to the extent of 74% of the instilled dose. In addition, a minimum of 5-10 min prolongation of ocular contact time was determined to be necessary for significantly reducing systemic drug absorption and indirectly enhancing ocular drug absorption. The pharmaceutical implication of this finding is that ophthalmic vehicles such as polymeric inserts and gels would provide more favorable ocular to systemic drug absorption ratios than vehicles such as aqueous solutions and low-viscosity polymer solutions.

Absorption↗

PubMed1981

Relationship of the xylose absorption status of children in Bangladesh to their absorption of macronutrients from local diets.

We compared the results of xylose absorption tests from 31 asymptomatic Bangladeshi children with their ability to absorb macronutrients from cereal-vegetable diets, as determined by metabolic balance studies. The xylose test results ranged from 9.8 to 37.0% excretion of the ingested dose, with more than half of the values less than 20% excretion. Nevertheless, the apparent absorption of macronutrients during 7-day balance studies ranged from 89.8 to 97.7% of intake for carbohydrate, 81.7 to 98.7% for fat, and 47.3 to 78.9% for nitrogen. There was a statistically significant correlation between the xylose test results and apparent carbohydrate absorption for one diet group only (r = 0.76, p less than 0.05), but not between the xylose results and other indicators of intestinal function of nutrition status. We conclude that diminished absorption of xylose, which is commonly recognized among asymptomatic residents of the tropics, does not necessarily indicate impaired absorption of macronutrients from the customary diet. Therefore, tropical enteropathy may not have major nutritional significance for those individuals with manifestations of the syndrome.

Bangladesh↗

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↗