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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↗
PubMed1989

Morphologic and functional alterations in absorptive epithelial cells during L-tryptophan induced inhibition of net sodium and fluid absorption in the rat ileum.

L-Tryptophan (L-Trp) has been reported to suppress jejunal fluid and electrolyte transport in vitro, at a 20 mM concentration, whereas other amino acids enhance that absorption at the same concentration. The effect of L-Trp, glycine (Gly) and L-phenylalanine (L-Phe) on in vivo ileal and jejunal fluid and sodium transport, and their morphologic correlates, were investigated in the rat. In the ileum, morphology as well as fluid and sodium transport were more readily altered by L-Trp than in the jejunum. The ileal effects were rapid; morphologic and transport changes were seen within 2.5 minutes. The changes were stereospecific; they occurred only with the levo, but not with the dextro isomer of Trp. There was a concentration dependence; 20 mM levels of L-Trp were required, whereas lower concentrations of the amino acid often stimulated net absorption. Morphologic alterations produced by L-Trp were restricted to absorptive epithelial cells, whereas goblet cells appeared unaffected. Morphologically, L-Trp treatment led to the formation of clear basal vacuoles in ileal absorptive epithelial cells at 2.5 minutes, and extensive vacuolization and loss of the lumenal permeability barrier to macromolecules at 30 minutes. Since L-Trp can be hydroxylated in the small intestine, we assessed the effects of L-5 = OH tryptophan and 5-hydroxytryptamine on small intestinal transport and morphology in this experimental system. L-5-OH tryptophan inhibited fluid transport and produced some epithelial cell vacuolization. However, 5-hydroxytryptamine, which most severely decreased transport, had none of the morphologic effects of L-Trp. We hypothesize that L-Trp may inhibit transport as a result of its intracellular accumulation in absorptive epithelial cells.

Animals↗
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↗
PubMed1982

Studies on the absorption of practically water-insoluble drugs following injection V: Subcutaneous absorption in rats from solutions in water immiscible oils.

To elucidate the kinetics and mechanisms of subcutaneous absorption of practically water-insoluble drugs in oily solutions, the absorption behaviors of select azo dyes and other prototype agents were investigated by a local clearance method in the dorsum in intact rats. The absorption of the drug components appeared to be first-order. The first-order rate constant (k) was inversely proportional to the cube root of the injection volume. In more limited studies, essentially the same behavior was observed in the rat abdomen, and the difference in k between the dorsal and abdominal injections was slight. The comparison of k of a given compound from different oily vehicles showed that k was governed predominantly by the distribution coefficient (K) between the oily vehicle and the aqueous subcutaneous medium and depended little on the viscosity of the vehicle. This distributioning relationship was shown through correlation of the rate constants with in vitro distribution coefficients. A plot of log k versus log K for all the compounds tested was linear with a slope of approximately -0.7. This linear relationship allows adequate prediction of absorption rates of other drugs from oily vehicles. The observed subcutaneous absorption rates and behaviors are compared with previous results involving the intramuscular route.

Administration, Topical↗
PubMed1982

Studies on the absorption of practically water-insoluble drugs following injection VI: Subcutaneous absorption from aqueous suspensions in rats.

The absorption characteristics and kinetics of practically water-insoluble drugs following subcutaneous injection of their aqueous suspensions were investigated in intact rats by the local clearance method and compared with those following intramuscular injection reported previously. The plot of the cube root of the residual fraction of the drug in the injection site versus time gave a good linear relationship under various experimental conditions. The absorption rate constant (j) increased with decreasing particle size. This increase was remarkable in the region of mean particle diameter less than 2-3 micrometers, while it was gradual or slight in the region above this. This phenomenon was explained by the fact that the in vivo spreading of particles of more than approximately 3 micrometers was still more limited by the network of the fibrous tissues. Between j and the initial drug concentration (C0) or injection volume (V0), the practically important relationship j alpha C0g V0h (g = -0.66 and h = -0.32) could approximately be derived from the experimental results. Comparison of j values among various compounds with different solubility (C's) in saline but with similar colloidal properties (particle size distribution and sedimentation volume) showed that a log j versus log C's plot gave a nearly straight line with a slope of approximately 0.5. All the results observed for the subcutaneous absorption were similar to those for intramuscular absorption and could reasonably be explained by the kinetic model proposed for intramuscular absorption.

Animals↗
PubMed1988

Characterization of the oral absorption of beta-lactam antibiotics. I. Cephalosporins: determination of intrinsic membrane absorption parameters in the rat intestine in situ.

The oral absorption of five cephalosporin antibiotics, cefaclor, cefadroxil, cefatrizine, cephalexin, and cephradine, has been studied using a single-pass intestinal perfusion technique in rats. Intrinsic membrane absorption parameters, "unbiased" by the presence of an aqueous permeability (diffusion or stagnant layer), have been calculated utilizing a boundary layer mathematical model. The resultant intrinsic membrane absorption parameters are consistent with a significant carrier-mediated, Michaelis-Menten-type kinetic mechanism and a small passive component in the jejunum. Cefaclor colon permeability is low and does not exhibit concentration dependent behavior. The measured carrier parameters (+/- SD) for the jejunal perfusions are as follows: cefaclor, J*max = 21.3 (+/- 4.0), Km = 16.1 (+/- 3.6), P*m = 0, and P*c = 1.32 (+/- 0.07); cefadroxil, J*max = 8.4 (+/- 0.8), Km = 5.9 (+/- 0.8), P*m = 0, and P*c = 1.43 (+/- 0.10); cephalexin, J*max = 9.1 (+/- 1.2), Km = 7.2 (+/- 1.2), P*m = 0, and P*c = 1.30 (+/- 0.10); cefatrizine, J*max = 0.73 (+/- 0.19), Km = 0.58 (+/- 0.17), P*m = 0.17 (+/- 0.03), and P*c = 1.25 (+/- 0.10); and cephradine, J*max = 1.57 (+/- 0.84), Km = 1.48 (+/- 0.75), P*m = 0.25 (+/- 0.07), and P*c = 1.06 (+/- 0.08). The colon absorption parameter for cefaclor is P*m = 0.36 (+/- 0.06, where J*max (mM) is the maximal flux, Km (mM) is the Michaelis constant, P*m is the passive membrane permeability, and P*c is the carrier permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

A concise review: iron absorption--the mucin-mobilferrin-integrin pathway. A competitive pathway for metal absorption.

Newly identified iron binding proteins isolated from rat duodenal homogenates permit better understanding of iron absorption. Mucins bind iron at acid pH to keep iron soluble and available for absorption at the more alkaline pH of the duodenum; this explains iron deficiency following prolonged achlorhydria. Integrin (90/150 kD) was identified on the absorptive surface of enterocytes in association with radioiron and is believed to facilitate transit of iron through the microvillous membrane. Mobilferrin, a 56 kD iron binding protein, was isolated from enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrins in the apical cytoplasm. We postulate it accepts dietary iron from integrin and acts as the shuttle protein for iron in the cytoplasm. Since iron in enterocytes remains in equilibrium with body stores, we postulate mucosal iron uptake is regulated by the number of iron binding sites either occupied or unoccupied by iron on mobilferrin. Iron repletion of enterocytes from body stores is accomplished via transferrin receptors on the posterolateral membranes of enterocytes. Increased transfer of iron from blood into absorptive enterocytes occurs in iron replete animals to inhibit mucosal uptake of dietary iron. Little transfer of iron from plasma to enterocytes occurs in iron deficiency. Enhanced mucosal transfer of iron into the body occurs with increased body need for iron. The exact mechanism for mucosal transfer of iron into the plasma has not been defined but may also be mediated by an integrin.

Absorption↗
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↗
PubMed1980

Absorption of sodium gamma-hydroxybutyrate and its prodrug gamma-butyrolactone: relationship between in vitro transport and in vivo absorption.

A qualitative relationship between in vitro transport and in vivo absorption of sodium gamma-hydroxybutyrate and gamma-butyrolactone was demonstrated. As with other short-chain acids, sodium gamma-hydroxybutyrate showed capacity-limited transport in vitro, consistent with the previous observation that this drug exhibited slower in vivo absorption with increasing dose. The prodrug lactone, on the other hand, showed a higher intestinal flux than the acid in the everted gut, and in vivo absorption also was more rapid. Capacity-limited transport and absorption of the lactone appeared less evident. Thus, the increased oral hypnotic activity of the lactone over that of the acid most likely is a result of its more favorable intestinal transport characteristics.

4-Butyrolactone↗
PubMed1984

Vaginal absorption of a potent luteinizing hormone-releasing hormone analogue (leuprolide) in rats. IV: Evaluation of the vaginal absorption and gonadotropin responses by radioimmunoassay.

The vaginal absorption of leuprolide (a potent luteinizing hormone-releasing hormone analogue), which has the potential for producing regression of hormone-dependent tumors as well as high gonadotropin-releasing and ovulation-inducing activities, was evaluated in rats by radioimmunoassay. Gonadotropin (luteinizing hormone and follicle-stimulating hormone) release was concomitantly determined. Although leuprolide disappeared rapidly from the serum after intravenous administration (the biological half-lives were 8.4 min in the alpha-phase and 33.2 min in the beta-phase), long-lasting serum levels were observed when the analogue was administered vaginally. The vaginal absorption was enhanced by adding citric acid to the test solution. The absolute bioavailability, estimated by the AUC of serum leuprolide levels, was 25.8% over 6 h and 38.0% over 12 h in the 5% citric acid solution (pH 3.5). The sustained release of gonadotropin was also obtained after vaginal administration of the analogue. A linear dose absorption correlation of leuprolide was obtained in the range of 10-1000 micrograms/kg in an aqueous solution or methylcellulose jelly. The release of gonadotropin showed a plateau level at greater than 10 micrograms/kg, which corresponds to an effective dose for antitumor activity. The vaginal absorption of leuprolide varied with the estrous cycle, but this effect was eliminated by prior subcutaneous pretreatment with the analogue.

Absorption↗
PubMed1984

Physical model approach to gastrointestinal absorption of prostaglandins II: In situ rat intestinal absorption of dinoprost.

In situ absorption studies with dinoprost in the rat jejunum were carried out using a modified Doluisio technique. The absorption rate was first order. There was a sigmoidal decrease in the rate with increasing buffer pH (from 3.5 to 9.5), which strongly indicated the partitioning of weak acid species into the lipoidal membrane. An asymptotic minimum rate was attained from buffer pH 7.5 to 9.5, operationally indicative of transport of anions across aqueous pores. The importance of the aqueous diffusion layer on the mucosal side of the membrane was evident; rates at pH 3.5 and 4.5 were faster at high agitation hydrodynamics in the lumen solution. Preliminary studies showed that there was no metabolism in the lumenal solution and that metabolism occurred within the membrane. The transport mechanism involved simultaneous passive diffusion and bioconversion in the membrane because (a) a 1.5 X 10(4)-fold range in dinoprost concentration (0.014-210 microM) showed no saturable carrier-mediated tendency on the rate, (b) iodoacetic acid and indomethacin did not inhibit the absorption rate, and (c) the shape of the absorption-pH profiles was suggestive of passive diffusion. The prostaglandin did not have apparent adverse membrane and vascular effects under the conditions employed. The quantification and factorization of the physically meaningful transport parameters were accomplished using the physical model previously described. The permeability coefficients of the aqueous diffusion layer for the oscillation and static hydrodynamic situations were 0.8 X 10(-4) and 1.7 X 10(-4) cm/s, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Improvement of systemic absorption of insulin through eyes with absorption enhancers.

A painless, simple, and practical method has been developed for systemic delivery of peptide drugs through eyes. In order to increase the amount of peptides absorbed into systemic circulation, effects of enhancers on insulin absorption into systemic circulation and reduction of blood glucose concentration have been studied. Saponin showed the highest potency to enhance insulin absorption, while Tween 20 was the least effective. The efficacy order of seven compounds studied can be arranged as follows: saponin greater than fusidic acid greater than BL-9 = EDTA greater than glycocholate = decamethonium greater than Tween 20. Since 1% of saponin reached the maximum effect to enhance insulin absorption and decrease blood glucose concentration, not more than 1% of saponin should be used for enhancing peptide absorption through eyes.

Absorption↗
PubMed1992

Adaptive computer program for determination of absorption profiles by numerical deconvolution: application to amoxicillin absorption.

We have developed a specific numerical deconvolution program for the Apple Macintosh microcomputer. After comparison with other methods, we used the program to evaluate the influence of nifedipine on the absorption and bioavailability of amoxicillin. The technique provided a model-independent approach. This study shows that the simultaneous administration of nifedipine with amoxicillin leads to a significant increase in both the total quantity of amoxicillin absorbed (+22%) and the rate of absorption. Parameters of clearance, volume of distribution, and elimination were unaffected. Numerical deconvolution analysis showed that nifedipine did not modify the absorption kinetics of amoxicillin, which are characterized by a lag time followed by a constant rate of absorption, suggesting zero-order kinetics with first-order kinetics at the end of the process. The results suggest the existence of a specialized, saturable transport molecule for this antibiotic.

Adult↗
PubMed1978

Iron absorption in patients with polycythemia vera: a comparative study using the whole-body counter and the ferrous sulfate absorption test.

The absorption of iron given per os to ten polycythemic patients was examined by two methods: first by giving radioactive iron (59Fe) and utilizing a whole-body counter, and second by peroral administration of ferrous sulfate. A correlation of 80% was achieved by the two methods. A comparison was made between the patterns of the ferrous sulfate absorption in the polycythemic patients and in five patients with low iron serum due to bleeding hemorrhoids. No difference was observed between these two groups, with the exception of the initial values which were lower in the polycythemic patients. On the other hand, the absorption of iron was higher in polycythemic patients, indicating that serum iron level is not the only factor regulating iron absorption.

Absorption↗
PubMed1986

New method of testing for carbohydrate absorption in man. Xylose and sucrose absorption; effects of sucrase inhibition.

Absorption of carbohydrate was quantitated in 49 subjects without disease of the small bowel using a new technique for ileal perfusion. A double-lumen tube with an attached balloon was inserted retrograde through the colon and used to quantify arrival in the ileum of D-xylose and a nonabsorbable marker which had been taken orally. In the same way, absorption of sucrose and the effects of an inhibitor of alpha-glucosidase were also studied. Insertion of the assembly through the colon and intubation of the terminal ileum was usually possible within 30 min; we have designated the technique, endoscopic retrograde bowel insertion (ERBI). The test meals were 500 ml of water containing either 25 g D-xylose and 5 g polyethylene glycol (PEG 4000), or 100 g sucrose with 5 g PEG. Sucrose meals also contained 0, 100, or 200 mg of an inhibitor of alpha-glucosidase (BAYg5421). At the end of a 5-hr test period, the ratio of recovery of D-xylose relative to that of PEG indicated that 69% of D-xylose was absorbed. Five-hour urinary excretion of D-xylose was 31% of that ingested, or 45% of the D-xylose which was absorbed. Sucrose was recovered in ileal samples only when administered together with inhibitor. Rates of sucrose absorption with BAYg5421, 100 and 200 mg, were 75% and 65%, respectively. The perfusion technique of ERBI is a rapid and reproduceable approach to the distal small intestine of man which could be of value in the investigation of intestinal absorption.

Acarbose↗
PubMed1977

Intestinal oxalate absorption. I. Absorption in vitro.

Enteric hyperoxaluria and oxalate urolithiasis in patients with ileal resection seem to be caused by intestinal hyperabsorption of oxalate. The mechanism responsible for hyperabsorption of oxalate is not known. Intestinal transport of oxalic acid was therefore examined by an in vitro technique in rat intestine. Oxalic acid was absorbed by a mechanism of simple passive diffusion. The rate of absorption decreased from the colon to the duodenum (colon greater than ileum greater than jejunum greater than duodenum). Bile acids enhanced oxalic acid absorption in the large and small intestine and increased extracellular space; calcium, however, markedly decreased mucosal-serosal transport of oxalic acid. Cholestyramine known to reduce oxalate excretion in hyperuxaluria associated with ileal resection did not directly affect absorption of oxalic acid, but decreased the enhanced absorption of oxalic acid induced by bile acids. The results suggest that the beneficial therapeutic effect of cholestyramine in hyperuxaluria is rather mediated by its bile acid binding activity than by direct binding of oxalic acid.

Animals↗
PubMed1991

Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid, and their effect on cholesterol absorption in rats.

The effects of various structured triglycerides containing medium-chain (caprylic or capric acids) and long-chain (linoleic acid) fatty acids on fatty acid and cholesterol absorption were studied in lymph-cannulated rats. A considerable portion of capric and caprylic acid was absorbed through the lymph duct, although to a lesser extent than was linoleic acid. Capric and linoleic acid located at the 2-position of 2-decanoyl-1,3-dilinoleoyl-glycerol (18:2/10:0/18:2) and 2-linoleoyl-1,3-didecanoyl-glycerol (10:0/18:2/10:0), respectively, tended to be absorbed more efficiently than those located at the 1- and 3-position or those from tricaprin (10:0/10:0/10:0) or trilinolein (18:2/18:2/18:2). A similar trend was observed when the medium-chain fatty acid was caprylic acid instead of capric acid. Caprylic acid absorption from 2-octanoyl-1,3-dilinoleoyl-glycerol (18:2/8:0/18:2) was significantly greater (p less than 0.05) than from 2-linoleoyl-1,3-dioctanoyl-glycerol (8:0/18:2/8:0) or tricaprylin (8:0/8:0/8:0). Preferential absorption of caprylic and linoleic acid was not observed when the 1 to 2 and the 2 to 1 mixtures of 8:0/8:0/8:0 and 18:2/18:2/18:2, respectively, were administered. The structured lipids did not affect the lymphatic absorption of cholesterol. The results suggest that structured triglycerides composed of medium-chain fatty acids and linoleic acid may be more useful for the treatment of lipid malabsorption than are mixtures of medium-chain triglyceride (MCT) and long-chain triglyceride (LCT).

Absorption↗