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PubMed1982

Synthetic human gastrin I and gastrin-like pentapeptide in studies of intestinal absorption in man. Role of gastrin in human intestinal absorption.

The effects of synthetic human gastric I (SHG I) and gastrin-like pentapeptide (PG) on jejunal water, electrolyte, and glucose absorption were studied in 11 normal subjects. The i.v. administration of graded doses of SHG I increased plasma gastrin levels similar to those after food intake and in the Zollinger-Ellison syndrome. SHG I and PG caused no significant changes in the net movement of water and solute. The findings indicate that gastrin has no direct effect on intestinal absorption in normal man, and does not account for the mechanism of diarrhea in the Zollinger-Ellison syndrome.

Adult↗
PubMed1997

Permethrin absorption not detected in single-pass perfused rabbit ear, and absorption with oxidation of 3-phenoxybenzyl alcohol.

Isolated rabbit ears were single-pass perfused with a protein-free medium. Permethrin (0.05-23.5%, w/w) was applied in four distinct ointments. Permethrin, 3-phenoxybenzyl alcohol, 3-phenoxybenzaldehyde, and 3-phenoxybenzoic acid were analysed by HPLC. Permethrin was not detected in the effluent. The permeation coefficient, calculated from the detection limit was < 7.3 x 10(-12) (cm/sec). The appearance rate of the 3-phenoxybenzyl moieties in the effluent agreed with the absorption of the corresponding impurities in the various ointments. In supernatant of homogenised skin, the hydrolysis rate of permethrin was linear; about 4 pmol/min per cm2 at 10 microM substrate concentration. The proportion of 3-phenoxybenzoic acid, a further metabolite of 3-phenoxybenzyl alcohol increased when an oxidizing co-factor system was added. The appearance rate in the effusate of 3-phenoxybenzyl alcohol following the lipophobic ointment was five times faster than from isopropyl myristate. The formation rate of 3-phenoxybenzoic acid followed saturation kinetics. Occupational systemic poisoning by dermal absorption of permethrin seems very unlikely since humans bear more epithelial cell layers than rabbits. These experiments do not contradict, however, possible paraesthesia during systemic poisoning after inhalation or ingestion of the pyrethroid-containing aerosols used in agriculture.

Animals↗
PubMed1977

Iron absorption in infants: high bioavailability of breast milk iron as indicated by the extrinsic tag method of iron absorption and by the concentration of serum ferritin.

Breast feeding is thought to result in a lower incidence of iron deficiency than does the use of unfortified cow milk forumalas, but there is scant documentation for this belief. The relationship of breast and cow milk feeding to absorption of iron and to iron status was investigated in a total of 45 term infants at about six months of age. Iron absorption was measured by total body counting. Laboratory assessment of iron status was based on the serum ferritin, hemoglobin, mean corpuscular volume, and transferrin saturation. The results indicated that infants fed breast milk during the entire first six to seven months of life attained greater iron stores than did those fed a cow milk formula. Breast-fed infants absorbed an average of 49% of a trace dose of extrinsic iron administered during a breast feeding in contrast to about 10% reported to be absorbed from cow milk under similar conditions. The data indicate that term infants who are breast fed may not require routine administration of supplemental iron.

Animals↗
PubMed1990

Solute absorption from the airways of the isolated rat lung. III. Absorption of several peptidase-resistant, synthetic polypeptides: poly-(2-hydroxyethyl)-aspartamides.

A series of samples of the synthetic polypeptide poly-alpha, beta-[N(2-hydroxyethyl)-DL-aspartamide] (PHEA), containing covalently bound fluorophore, ethylcarbonyl-6-aminofluorescein, and exhibiting different molecular weight distributions with weight average molecular weights ranging from approximately 4 to 43 kD, was prepared and characterized. Aqueous solutions of the polymers were administered to the airways of isolated perfused rat lung preparations, and transfer to the perfusate was measured. Polymers administered directly to the perfusate were not degraded during the experiment. Polymer transfer rates were dependent upon starting molecular weight distribution, larger molecules being absorbed more slowly. In the case of a polymer with a median molecular weight of 7.2 kD, the absorbed species appeared to be smaller molecules than those which were originally administered. This was not the case for a 3.98-kD polymer; absorbed material had a gel permeation chromatography elution volume equivalent to that of the administered material. Absorption for the 3.98-kD polymer was found to be dose dependent. Approximately 70% absorption of a 0.2-mg dose occurred in 100 min. Much larger polymers (up to 11.65 kD) were also absorbed at finite rates. Results are discussed in the context of macromolecular delivery to the systemic circulation via the lung.

Absorption↗
PubMed1994

Oral absorption of peptides: the effect of absorption site and enzyme inhibition on the systemic availability of metkephamid.

In this study the intestinal degradation and absorption of a synthetic pentapeptide, metkephamid, were investigated in the rat by determination of its wall permeabilities in the small and large intestine and the extent and mechanism of its intestinal degradation. The peptide was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane. The extent of metabolic inactivation depended on the intestinal segment investigated and decreased in the axial direction. No metabolism was found in the colon. The dimensionless wall permeabilities (Pw*), determined by single-pass perfusion, were also site dependent. Pw* was highest in the ileum [1.91 +/- 0.24, (SE); n = 4], followed by the jejunum (1.64 +/- 0.34; n = 4) and the colon (0.67 +/- 0.38; n = 4). Based on the permeability data alone and under the assumption of no presystemic metabolism, complete bioavailability would be predicted for metkephamid. However, following oral administration, the mean absolute bioavailability was only 0.22 +/- 0.065% (n = 3), indicating the overall dominance of degradation in the absorption process. Thus future strategies in oral peptide delivery should focus on increasing the stability of the peptide in the intestine by modifying the peptide structure and/or delivering the compound to an intestinal segment showing little or no enzymatic degradation.

Amino Acid Sequence↗
PubMed1994

Cyclodextrins as mucosal absorption promoters of insulin. II. Effects of beta-cyclodextrin derivatives on alpha-chymotryptic degradation and enteral absorption of insulin in rats.

The relative effectiveness of two beta-cyclodextrin derivatives, i.e., dimethyl-beta-cyclodextrin (DM beta CD) and hydroxypropyl-beta-cyclodextrin (HP beta CD), in enhancing enteral absorption of insulin was evaluated in the lower jejunal/upper ileal segments of the rat by means of an in situ closed loop method. The incorporation of 10% (w/v) DM beta CD to a 0.5 mg/ml porcine-zinc insulin solution dramatically increased insulin bioavailability from a negligible value (approximately 0.06%) to 5.63%, when administered enterally at a dose of 20 U/kg. However, addition of 10% (w/v) HP beta CD did not improve enteral insulin uptake significantly with a bioavailability of only 0.07%. Similarly, the pharmacodynamic relative efficacy values obtained after the enteral administration of 20 U/kg insulin, 20 U/kg insulin with 10% HP beta CD, and 20 U/kg insulin with 10% DM beta CD were 0.24%, 0.26%, and 1.75%, respectively. Biodegradation studies of 0.5 mg/ml insulin hexamers by 0.5 microM alpha-chymotrypsin revealed no inhibitory effect on the enzymatic activity by the two cyclodextrins. On the contrary, the apparent first-order rate constant increased significantly in the presence of 10% DM beta CD, suggesting insulin oligomer dissociation by DM beta CD. Histopathological examination of the rat intestine was performed to detect tissue damage following enteral administration of the beta-cyclodextrin derivatives. Light microscopic inspection indicated no observable tissue damage, thereby arguing direct membrane fluidization as the primary mechanism for enhanced insulin uptake. This study indicates the feasibility of using cyclodextrins as mucosal absorption promoters of proteins and peptide drugs.

Administration, Oral↗
PubMed1985

Food-induced changes in theophylline absorption from controlled-release formulations. Part I. Substantial increased and decreased absorption with Uniphyl tablets and Theo-Dur Sprinkle.

Food-induced changes in absorption from two controlled-release formulations of theophylline (Uniphyl tablets [Purdue Frederick Co.] and Theo-Dur Sprinkle [Key Pharmaceuticals, Inc.]) were studied in healthy male nonsmokers. Although the two forms exhibited a theophylline in vitro dissolution rate that was independent of changes in pH from 1 to 8, they showed substantial but opposite food-induced absorption changes. In a 12-subject, three-way, single-dose, randomized, crossover study the bioavailability of theophylline relative to immediate-release aminophylline tablets increased from 53% +/- 23% (means +/- SD) to 96% +/- 46% when Uniphyl (two 400 mg tablets) was taken under fasting and nonfasting (high fat content meal) conditions, respectively. On the other hand, in a separate six-subject, two-way, randomized, crossover study, food reduced the bioavailability of theophylline from Theo-Dur Sprinkle: Theophylline bioavailability in the nonfasting state was only 53% +/- 9% that in the fasting state.

Absorption↗
PubMed2004

Photophysical properties of a carbazolyl mesogen of 8PCzC as revealed by absorption, fluorescence, and transient absorption measurements.

Fluorescence spectra in three phases [crystalline, smectic A liquid crystal (SmA), and isotropic] of a mesogen including one carbazolyl (Cz) chromophore, 4'-n-octylphenyl carbazole-2-carboxylate (8PCzC), were measured at various temperatures and compared with fluorescence spectra in solvents with various dielectric constants. Further, for the first time, picosecond transient absorption spectroscopy was applied to elucidating photoinduced electron-transfer dynamics (charge separation, charge recombination, and hole transfer reactions) in the three phases of 8PCzC doped with a small amount of an electron acceptor. The fluorescence spectra showed clearly the presence of two crystalline phases, which was supported by DSC measurement. On the basis of a comparison of the fluorescence spectra and those in solution, the 8PCzC molecule in the first crystal structure was suggested to be in polar environment compared to that in the second one. The fluorescence yields of 8PCzC in both SmA and isotropic phases were remarkably small compared to that in crystalline one. This was ascribed to the formation of hydrogen bonds between 8PCzC molecules in both SmA and isotropic phases. As a first approximation, the picosecond transient absorption spectra in the three phases of 8PCzC doped with 2,4,7-trinitrofluorenone were analyzed by the simple model of one-dimensional hole migration. The rate constants obtained for the hole transfer from the cation state of Cz chromophore to neighboring Czs decreased in the order of SmA (approximately 10(9) s(-1)) > isotropic (approximately 10(8) s(-1)) > crystalline (approximately 10(7) s(-1)) phases, although these measurement temperatures were different.

Absorption↗
PubMed1999

Metabolism of pamaqueside, a cholesterol absorption inhibitor, in Long-Evans rat: effect of bile duct cannulation on absorption.

The metabolism of pamaqueside, a cholesterol absorption inhibitor, was studied in the bile duct cannulated and non-cannulated rat after an oral dose (100 mg/kg) and an i.v. dose (6 mg/kg) of [14C]pamaqueside. Faeces was the major route of excretion in all rat. Only 0.1% of the radioactivity was recovered in the urine of the non-cannulated rat. In contrast, approximately 17% of the total dose was recovered in the bile and urine in the bile duct cannulated rat. Following an i.v. dose, an almost equal percentage of radioactivity was excreted in the bile and urine of the bile duct cannulated rat. 3. The aglycone (M1) was the major metabolite in rat and was present in greater amounts in the faeces of the bile duct cannulated rat. The structural elucidation of metabolites in the bile and urine indicated that M1 was metabolized oxidatively via a novel ring opening, and the oxidative metabolites further underwent sulphate conjugation. The oxidative ring opening of pamaqueside (the cellobioside ring intact) was also observed following an i.v. dose to rat suggesting that oxidative ring opening was the major route of metabolism of saponins, at least in rat. The study demonstrated that the absorption and metabolism of pamaqueside was altered by surgical cannulation of rat.

Animals↗
PubMed1950

Radioiron absorption in anemic dogs; fluctuations in the mucosal block and evidence for a gradient of absorption in the gastrointestinal tract.

The control of iron absorption appears to reside in the mucosa of the gastrointestinal tract. The normal dog absorbs very little iron, but the anemic iron-depleted dog may absorb 10 to 20 times as much. This "mucosal block" of the normal dog probably is due largely to iron stores in the mucosa. "Mucosal block" can be effected in the anemic iron-depleted dog by feeding of iron salts, but the degree of "mucosal block" under these conditions never reaches the high degree of "mucosal block" in the normal dog. Rapid movement of iron through the mucosa may explain the short duration of "mucosal block" due to iron feeding in the anemic iron-depleted dogs (18 to 20 hours, Fig. 1). The colon absorbs very little iron under the conditions described. The stomach and duodenum seem to be most active in its absorption. This suggests the existence of a gradient in the capacity of the gastrointestinal tract to absorb iron.

Anemia↗
PubMed1998

Calcium absorption--a paradigm for mineral absorption.

Intestinal calcium absorption proceeds by two mechanisms, an active transcellular process that takes place in the duodenum and a passive paracellular process throughout the small intestine. This article characterizes the three steps of transcellular calcium movement-entry, intracellular diffusion and extrusion-and identifies conditions that must be satisfied for other mineral ions to move transcellularly as part of a transepithelial transport process. Passive calcium movement is down a chemical gradient with the amount absorbed by this pathway determined in large measure by the sojourn time, most of which is spent in the ileum. Because transcellular movement of most mineral ions other than calcium, where measured, is either small or negligible, passive transport is likely to be the major route of intestinal absorption, the nature of which, however, has not been well established experimentally.

Animals↗
PubMed1976

Serum iron increase as a measure of iron absorption - studies on the correlation with total absorption.

The correlation between the magnitude of the increase of serum iron after an oral dose of iron and the total absorption of iron was studied in 51 healthy subjects and 10 patients with iron deficiency anaemia. 59Fe-labelled solutions of ferrous sulphate (25-100 mg iron) were administered to the fasting subjects. The serum iron concentration was followed for 4-6 hours and the absorption was measured in a whole-body counter. Good correlation was found between the maximal increase of serum iron and the total amount of iron absorbed after a dose of iron given as a solution. The serum iron method may be used for comparisons of the absorbability of different doses of iron by performing cross-over studies in groups of subjects. However, it was found that in an individual subject the serum iron method could not be used to determine the amount of iron absorbed from an oral dose of iron.

Administration, Oral↗
PubMed1972

Observations on folate absorption with particular reference to folate polyglutamate and possible inhibitors to its absorption.

A test system for detection of inhibitors to the enzyme which removes the glutamic acid peptide chain from folate polyglutamates (folate conjugase) is described. This utilizes the reaction between plasma conjugase and the folate polyglutamate in red blood cell haemolysate. Diphenylhydantoin and yeast extracts did not inhibit plasma conjugase. The better absorption of monoglutamate forms of folate as compared to polyglutamate forms was confirmed. Polyglutamates were absorbed normally by patients with pernicious anaemia, suggesting that conjugase enzymes (optimally active at pH 4.5) did not normally function to a significant extent in the gut lumen. Diphenylhydantoin and bicarbonate did not interfere with absorption of either mono- or polyglutamate forms of folate.

Anemia, Pernicious↗
PubMed2006

Molecular characterisation of non-absorptive and absorptive enterocytes in human small intestine.

BACKGROUND AND AIMS: Perturbation of differentiation of the crypt-villus axis of the human small intestine is associated with several intestinal disorders of clinical importance. At present, differentiation of small intestinal enterocytes in the crypt-villus axis is not well characterised. SUBJECTS AND METHODS: Expression profiling of microdissected enterocytes lining the upper part of crypts or the middle of villi was performed using the Affymetrix X3P arrays and several methods for confirmation. RESULTS: A total of 978 differentially expressed sequences representing 778 unique UniGene IDs were found and categorised into four functional groups. In enterocytes lining the upper part of crypts, cell cycle promoting genes and transcription/translation related genes were predominantly expressed, whereas in enterocytes lining the middle of villi, high expression of cell cycle inhibiting genes, metabolism related genes, and vesicle/transport related genes was found. CONCLUSION: Two types of enterocytes were dissected at the molecular level, the non-absorptive enterocyte located in the upper part of crypts and the absorptive enterocyte found in the middle of villi. These data improve our knowledge about the physiology of the crypt-villus architecture in human small intestine and provide new insights into pathophysiological phenomena, such as villus atrophy, which is clinically important.

Adult↗
PubMed1993

Rectal absorption of acyclovir in rats and improvement of absorption by triglyceride base.

The rectal absorption of acyclovir has been evaluated after administration of suppositories without absorption enhancers in rats. The disappearance of plasma acyclovir followed biexponential kinetics after i.v. dosing. Rectal administration of a triglyceride (Vosco S-55 and Vosco S-55 + methylcellulose) suppository gave relatively high plasma concentrations and bioavailabilities (95.3 and 83.4%, respectively) compared with Witepsol and macrogol suppositories. However, the in vitro release profiles from suppositories did not accurately reflect plasma concentrations after rectal dosing. Our results suggest that the rectal administration of acyclovir suppositories may be a promising substitute for intravenous infusion, which is at present used for the treatment.

Acyclovir↗
PubMed1995

Intestinal absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue. II. In situ and in vitro absorption characteristics of azetirelin from the rat intestine.

Intestinal absorption characteristics of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, were studied in rats by means of in situ closed loop and in vitro everted sac experiments. Plasma concentrations of azetirelin obtained in the in situ closed loop experiments were not significantly different among the intestinal segments. Area under the plasma concentration-time curve (AUC) of azetirelin following administration into the duodenal loop increased in proportion to the dose. The serosal to mucosal concentration ratio of the analogue in the everted sac experiment was constant over the mucosal drug concentration range of 0.01-10 mM. There was no directional difference in the transfer rate of azetirelin across the everted and non-everted sacs of the duodenum. Furthermore, its transport across the duodenum was not influenced by low incubation temperature (25 degrees C), addition of dipeptide (Gly-Gly), or pretreatment of the mucosal surface with 2,4-dinitrophenol, while that of TRH was inhibited under these conditions. These results suggest that the intestinal absorption mechanism of azetirelin is different from that of TRH, and that azetirelin is predominantly transported via a passive diffusion.

Amino Acid Sequence↗
PubMed1992

Percutaneous absorption of ketoprofen from acrylic gel patches containing d-limonene and ethanol as absorption enhancers.

The percutaneous absorption of ketoprofen (KPF) from gel patches containing d-limonene and ethanol was investigated in rats. Plasma levels of KPF varied with the kind of polymers which constitute the gel patch, and the highest level was observed when the copolymer of ethylacrylate (EA) and diethyleneglycolmethacrylate (DEGMA) was used as a vehicle. The amount of KPF permeating through the rat skin from the gel patch was well correlated with that of ethanol. Permeations were enhanced with increase in the amount of d-limonene distributed from the vehicle to the skin tissue. The amount of d-limonene accumulated in the skin varied greatly with the kind of polymers; the highest accumulation was observed with the EA-DEGMA copolymer, and decreased with increasing affinity of d-limonene to the polymers. The reason EA-DEGMA copolymer showed the highest percutaneous absorption of KPF from gel patches containing d-limonene may be the hydrophilic nature of this polymer which showed the lowest affinity to d-limonene.

Administration, Cutaneous↗