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PubMed1990

Combinative improving effect of increased solubility and the use of absorption enhancers on the rectal absorption of uracil in beagle dogs.

An improvement of the rectal absorption of uracil was examined by the application of absorption enhancers in addition to the increased solubility of uracil. Uracil was ground with additives such as MgO, sodium 2,6-dihydroxybenzoate, human serum albumin or hydroxypropylmethylcellulose acetate succinate. Aqueous, oily and powdery formulations, which consisted of the ground mixtures, nicotinamide, urea and absorption enhancers such as polyoxyethylene (23) cetylether (BC-23) or sodium caprate, were prepared. Uracil solubility in the aqueous formulations was increased about 4-13 times that in the corresponding control formulations. When rectally administered to beagle dogs, marked increases in the plasma uracil level were observed in some of the cases of aqueous and oily formulations. In the powdery formulations and formulations containing macromolecular additives, however, absorption improvements was not observed. The results indicated that an improvement in the absorption of uracil was caused by the combinative improving effect of the increased uracil solubility and the promoting effect of absorption enhancers.

Absorption↗
PubMed1990

Studies on sustained-release suppositories. III. Rectal absorption of morphine in rabbits and prolongation of its absorption by alginic acid addition.

Rectal absorption of morphine from various kinds of suppository bases was investigated. The extent of bioavailability of morphine by rectal administration varied with the bases used (30.5-97.5%), but every value was higher than that in the case of oral administration (13.5%). Witepsol bases were preferable to macrogol base for the rectal absorption of morphine. In particular, Witepsol S-55 or W-35 gave a higher plasma peak level than H-15 or E-75, whereas the difference in the mean residence times obtained from these bases could not be regarded as significant. Sustained-release suppositories of morphine could be prepared simply by mixing alginic acid (Alg) with morphine in a suppository base. Further, prolonged rectal absorption could be obtained by using these sustained-release suppositories, and the absorption rate was controlled by the amount of Alg added. It seems likely that the sustained release was due to the binding of morphine to Alg from the results of partition coefficient and binding ratio measurements in aqueous solution. The rapid initial absorption and the subsequent prolonged absorption of morphine simultaneously obtained from the morphine-Alg suppository may be useful in the clinical context.

Alginates↗
PubMed1977

Intestinal absorption of alpha-tocopherol in the unanesthetized rat. The influence of luminal constituents on the absorptive process.

3H-alpha-tocopherol intestinal absorption was studied in the unanesthetized rat. The rate of alpha-tocopherol absorption remained linear over a wide range of concentrations (4 nM to 400 micrometer). Increasing the sodium taurocholate concentration in the micellar infusate up to 15 mM did not increase the rate of absorption of the vitamin. Addition of long-chain fatty acids to the micellar infusate decreased the absorption rate of the vitamin (p less than 0.05). The decrease was most significant (p less than 0.01) following the addition of the polyunsaturated linolenic (C18:3) acid. Increasing the hydrogen ion concentration in the perfusate increased the absorption rate of alpha-tocopherol. The present experiments in vivo support the conclusions drawn from in vitro uptake experiments which indicated that alpha-tocopherol is absorbed by a passive diffusion process. These experiments indicate that micellar expansion with polyunsaturated fatty acids interferes with the absorption of alpha-tocopherol and may result in deficiency of the vitamin.

Animals↗
PubMed1990

Bile salt-fatty acid mixed micelles as nasal absorption promoters of peptides. I. Effects of ionic strength, adjuvant composition, and lipid structure on the nasal absorption of [D-Arg2]kyotorphin.

Bile salts and synthetic surfactants have been used to promote nasal absorption of peptide drugs. Although a marked increase in nasal absorption has been achieved, this may not be adequate and the possibility of adjuvant-induced membrane toxicity exists. The present study employs a rat in situ nasal perfusion technique and mixed micelles between sodium glycocholate (NaGC) and various lipids as potential nasal absorption enhancers of a stable model dipeptide, [D-Arg2]kyotorphin. NaGC alone enhanced the nasal absorption of the dipeptide in a concentration-dependent manner. When linoleic acid was added to form mixed micelles with NaGC, the absorption was further enhanced (P less than 0.01). The effect of mixed micelles was synergistic and much greater than with single adjuvants. Increasing ionic strength was found to increase the adjuvant activity of both NaGC and NaGC-lipid mixed micelles. Structure of the lipid component of the mixed micelles also affected the adjuvant potency. Oleic acid, a cis-unsaturated fatty acid, was more effective than elaidic acid, the trans-isomer, whereas cis-linoleic acid and trans-linolelaidic acid were equally effective (alpha = 0.05). Mixed micelles of mono-glycerides such as monoolein and monolinolein were also more effective than NaGC alone (alpha = 0.05). Micellar solubilization of these polar lipids by NaGC appears to be important for nasal absorption enhancement to occur. Reversal of the membrane permeability was also observed within approximately 20-40 min after removal of the adjuvants from the rat nasal cavity. These observations are similar to the effects of mixed micelles on the rectal mucosa and may involve the same mechanism.

Adjuvants, Pharmaceutic↗
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↗
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↗
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↗
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↗
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↗
PubMed1978

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

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

Absorption↗
PubMed1976

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

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

Adolescent↗
PubMed1992

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

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

Absorption↗
PubMed1975

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

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

Adult↗
PubMed1990

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

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

Administration, Oral↗
PubMedDate not supplied

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

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

Amino Acids↗
PubMed1975

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

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

Amino Acids↗
PubMed1975

Effect of surfactants on absorption through membranes IV: effects of dioctyl sodium sulfosuccinate on absorption of a poorly absorbable drug, phenolsulfonphthalein, in humans.

To explore the effect of dioctyl sodium sulfosuccinate on drug absorption in humans, the urinary excretion of a poorly absorbable drug, phenolsulfonphthalein, administered in solution with and without the surfactant was determined. Coadministration of a therapeutic dose of the surfactant with the drug solution resulted in a significant increase in the initial rate of absorption. A small increase in the extent of absorption was also observed. Pretreatment with the surfactant for 6 nights, followed by administration of the drug on the 7th day, did not significantly change the rate of extent of absorption. The surfactant is thought to have a direct effect on the GI membrane, resulting in a temporary change in its permeability. This effect appears to be reversible after a few hours.

Adult↗