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PubMed1982

Maternal essential fatty acid supplementation increases zinc absorption in neonatal rats: relevance to the defect in zinc absorption in acrodermatitis enteropathica.

Pregnant zinc deficient and zinc adequate rats were injected subcutaneously with evening primrose oil throughout gestation and for 3 days post partum. The nursing pups were injected intragastrically with zinc-65 on day 3 of live and sacrifices 4 h later. The % of the total injected zinc recovered in the carcass (minus the gut and gut contents) was significantly increased in those pups nursed by mothers injected with evening primrose oil, regardless of their dietary zinc intake. The fatty acid composition of the total lipid extract of the gut and gut contents of the neonates with increased zinc-65 absorption indicated that these pups had higher proportions of arachidonic acid and other metabolites of linoleic acid than did those with lower zinc-65 absorption. In other 3-day-old rat pups, intragastric injection of linoleic, gamma-linolenic or dihomo-gamma-linolenic acids along with the dose of zinc-65 very significantly increased zinc-65 absorption in a dose-related manner. Arachidonic acid however had no significant effect on zinc-65 absorption. Prostaglandin E1 caused a significant increase in zinc-65 absorption but prostaglandin E2 had no consistent effect. Indomethacin caused a dose-related inhibition of zinc-65 absorption.

Acrodermatitis↗
PubMed2000

Intestinal absorption of octreotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo.

Octreotide acetate is a somatostatin analogue used for the control of endocrine tumors of the gastrointestinal (GI) tract and the treatment of acromegaly. The oral absorption of octreotide is limited because of the limited permeation across the intestinal epithelium. Both chitosan hydrochloride and N-trimethyl chitosan chloride (TMC), a quaternized chitosan derivative, are nonabsorbable and nontoxic polymers that have been proven to effectively increase the permeation of hydrophilic macromolecules across mucosal epithelia by opening the tight junctions. This study investigates the intestinal absorption of octreotide when it is coadministered with the polycationic absorption enhancer TMC. Caco-2 cell monolayers were used as an in vitro intestinal epithelium model, and male Wistar rats were used for in vivo studies. Octreotide with or without polymers (TMC; chitosan hydrochloride) was administered intrajejunally in rats, and serum peptide levels were measured by radioimmunoassay. All applications and administrations were performed at neutral pH values (i.e., pH = 7.4). In vitro transport studies with Caco-2 cells revealed an increased permeation of octreotide in the presence of TMC. Enhancement ratios ranged from 34 to 121 with increasing concentrations of the polymer (0.25-1.5%, w/v). In rats, 1.0% (w/v) TMC solution significantly increased the absorption of the peptide analogue, resulting in a 5-fold increase of octreotide bioavailability compared with the controls (octreotide alone). Coadministration of 1.0% (w/v) chitosan hydrochloride did not enhance octreotide bioavailability. These results in combination with the nontoxic character of TMC suggest that this polymer is a promising excipient in the development of solid dosage forms for the peroral delivery and intestinal absorption of octreotide.

Algorithms↗
PubMed1985

[Comparative studies on the enzymatic absorption of protein hydrolysates in the small intestines of the rat. 3. The absorption of trypsin, thermitatic and trypsin thermitatic wheat gluten hydrolysates in comparison with equimolar mixtures of free amino acids].

Tryptic, thermitatic, and tryptic-thermitatic wheat-gluten hydrolyzates as well as their equimolar amino-acid mixture 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 tryptic hydrolyzate showed a significantly lower absorption of nitrogen and total amino acids than the amino-acid mixture. Both the supplied forms were very different as to their absorption pattern of the amino acids. The high variability of the percental absorption of the individual amino acids of the tryptic hydrolyzate results in a high coefficient of variation. The absorption of nitrogen and total amino acids from thermitatic and tryptic-thermitatic hydrolyzates is equal to that from the amino-acid mixture. In a peptidic form glutamic acid is more rapidly absorbed from the two hydrolyzates, and methionine from the tryptic-thermitatic hydrolyzate in both the intestinal parts. As to alanine and glycine this concerns only the distal intestinal part for both the hydrolyzates. There are no differences between the absorption patterns of the two hydrolyzates but in comparison with the amino-acid mixture and the tryptic hydrolyzate differences were evident. The coefficients of variation of both the hydrolyzates are significantly lower as compared to those of the tryptic hydrolyzate and the amino-acid mixture. All forms of supply are more rapidly absorbed in the distal than in the proximal part of the intestine.

Amino Acids↗
PubMed1975

Percutaneous absorption of drugs. IV. Percutaneous absorption of drugs from oily vehicles.

The percutaneous absorption and retention of salicylic acid and carbinoxamine from four oily vehicles (liquid paraffin, oleic acid, hexadecyl alcohol, and isopropyl myristate) were studied by employing a recirculation apparatus. The absorption followed first-order kinetics, with the exception of the initial period. The vehicle that had a strong affinity to the drug showed a poor drug-releasing effect, and poor absorption and retention of drugs by the skin were observed. Higher absorption rate constants were observed for damaged skin than intact skin. The acceleration of absorption because of skin damage, however, was not so great from liquid paraffin as from the aqueous solution. The amount of drugs retained in the damaged skin declined following the initial increase.

Animals↗
PubMed1984

Physical model approach to gastrointestinal absorption of prostaglandins III: In situ rat intestinal absorption of dinoprostone.

In situ absorption studies with dinoprostone in the rat jejunum were carried out to provide a quantitative mechanistic insight of the absorption process. The variables included buffer pH (3.5-9.5), buffer capacity, hydro-dynamics in the lumen, and concentration. The disappearance kinetics from the lumen was first order. The rate decreased with increasing pH in a sigmoidal manner and reached a minimum at about pH 9. These results indicate the effects of the partitioning of nondissociated species in the lipoidal membrane and transport across aqueous pores. The rate was higher with the higher degree of agitation of the lumenal solution. Between two hydrodynamic situations, the differences in the rates were large at pH 4.5 where the transport was largely aqueous diffusion controlled and then tended to become smaller with increasing pH where the transport became effectively membrane controlled. The 15-oxo- and 13,14-dihydro-15-oxo metabolites of dinoprostone were found. The physical model was applied to quantify the permeability coefficients of the aqueous diffusion layer and the aqueous pores of the membrane and the effective membrane transport-bioconversion permeability coefficient at various pH values. The overall absorption dinoprostone was similar to that of the less lipophilic dinoprost reported earlier and also more rapid. Hence, baseline absorption studies were completed with two major reference prostaglandins from which estimations of intestinal absorption can be made for their analogues and derivatives.

Animals↗
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↗
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↗
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↗