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At least 91 records · Page 5Linked to original sources
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↗
PubMed1991

Percutaneous absorption of parathion in vitro in porcine skin: effects of dose, temperature, humidity, and perfusate composition on absorptive flux.

The effect of environmental factors on the percutaneous absorption of parathion in excised porcine skin was assessed in a flow-through diffusion cell system by varying the temperature (T), relative humidity (%RH), perfusate flow rate (F), and composition (porcine serum) at three parathion doses (4, 40, and 400 micrograms/cm2) compared to standard conditions (air temperature = 37 degrees C, perfusate temperature = 37 degrees C, %RH = 60, flow rate = 4 ml/hr, and standard bovine serum albumin medium). Parathion absorption was assessed by monitoring total radiolabeled activity appearing in the perfusate over time. High relative humidity significantly increased parathion penetration, as did two elevated temperature conditions. The effects of flow rate and perfusate composition were variable and dose dependent. In the present studies, lower applied doses appeared to be more sensitive to changes in the environmental conditions studied. These results suggest that these parameters have independent and different degrees of effect on parathion percutaneous absorption. Experimental conditions should be strictly controlled and dose-response studies need to be conducted when evaluating transdermal studies. Finally, if similar effects occur in vivo, the risk assessment calculations on percutaneous absorption should take these parameters into consideration.

Animals↗
PubMed1976

Food iron absorption in human subjects. IV. The effects of calcium and phosphate salts on the absorption of nonheme iron.

The influence of physiological levels of calcium and phosphorus on the absorption of nonheme iron from a semisynthetic meal was evaluated. Each of the 34 participating subjects received two to four test meals. In three studies where both calcium and phosphate were added, absorption of nonheme iron was reduced to 27 to 47% of that absorbed when no salts were added. However, with the single addition of either calcium or phosphate to the test meals no significantly inhibiting effect was observed. As the absorption of nonheme iron was significantly reduced only with the combined addition of calcium and phosphate, it is suggested that a calcium-phosphate-iron complex forms which inhibits iron absorption.

Absorption↗
PubMed1976

Absorption from different types of iron tablets - correlation between serum iron increase in total absorption of iron.

The absorption of iron from three different iron tablets - rapidly-disintegrating ferrous sulphate and ferrous carbonate tablets and slow-release ferrous sulphate tablets - was studied in healthy subjects with a serum iron technique and by whole-body counter measurements. A solution of ferrous sulphate was used as a reference. There were no differences in the absorption from the ferrous sulphate preparations, but the ferrous carbonate tablets were less well absorbed. Good correlation was found between the maximal serum iron response and the total absorption of iron and it was concluded that serum iron studies may be used for semiquantitative measurements of iron absorption in comparative studies on different iron preparations.

Adult↗
PubMed1988

Absorption of bile acids in dog as determined by portal blood sampling: evidence for colonic absorption of bile acid conjugates.

The intestinal phase of enterohepatic circulation, such as site and state of bile acid absorption, along the length of the intestinal tract has been speculated but not directly quantitated. In order to gain insight into the actual state of intestinal absorption of bile acid, the bile acid composition of portal blood from various segments of the intestinal tract was studied in dogs after loading endogenous bile acid by injection of caerulein. Total and unconjugated bile acids were determined with and without enzymatic hydrolysis, respectively. The amount of conjugated bile acids was calculated by subtracting unconjugated from total bile acids. Quantitation of cholic, chenodeoxycholic, deoxycholic and lithocholic acids and their conjugates was carried out by gas chromatography/mass spectrometry/selected ion monitoring with deuterated bile acids as internal standards. The major site of absorption of taurine-conjugated bile acid, a major conjugate form in the dog, was the distal small intestine. In addition, a considerable amount of cholic acid was found to be absorbed from the distal large intestine, the majority of which was still in the conjugated form. The pronounced absorption of the unconjugated secondary bile acid from the large intestine suggests the very active formation of the secondary bile acid in situ.

Animals↗
PubMed1988

Bicarbonate absorption stimulates active calcium absorption in the rat proximal tubule.

To evaluate the effect of luminal bicarbonate on calcium reabsorption, rat proximal tubules were perfused in vivo. Perfusion solution contained mannitol to reduce water flux to zero. Total Ca concentration was measured by atomic absorption spectrometry, Ca ion concentration in the tubule lumen (CaL2+) and the peritubular capillary (CaP2+), and luminal pH (pHL) with ion-selective microelectrodes and transepithelial voltage (VTE) with conventional microelectrodes. When tubules were perfused with buffer-free Cl-containing solution, net Ca absorption (JCa) averaged 3.33 pmol/min. Even though VTE was 1.64 mV lumen-positive, CaL2+, 1.05 mM, did not fall below the concentration in the capillary blood, 1.07 mM. When 27 mM of Cl was replaced with HCO3, there was luminal fluid acidification. Despite a decrease in VTE and CaL2+, JCa increased to 7.13 pmol/min, indicating that the enhanced JCa could not be accounted for by the reduced electrochemical gradient, delta CCa. When acetazolamide or an analogue of amiloride was added to the HCO3 solution, JCa was not different from the buffer-free solution, suggesting that HCO3-stimulated JCa may be linked to acidification. To further test this hypothesis, we used 27 mM Hepes as the luminal buffer. With Hepes there was luminal fluid acidification and JCa was not different from the buffer-free solution but delta CCa was significantly reduced, indicating enhanced active calcium transport. We conclude from the results of the present study that HCO3 stimulates active Ca absorption, a process that may be linked to acidification-mediated HCO3 absorption.

Absorption↗
PubMed1988

Studies on intestinal lymphatic absorption of drugs. II. Glyceride prodrugs for improving lymphatic absorption of naproxen and nicotinic acid.

A series of alpha- and beta-monoglycerides and triglyceride derivatives of naproxen or nicotinic acid were synthesized and investigated in order to elucidate the molecular form of the derivative with properties that enhanced lymphatic absorption. The lymphatic absorption rate was increased by adjusting the length of an n-alkyl chain introduced between the alpha- or beta-position of glycerol and the drug residue. The alpha- and beta-monoglyceride derivatives (containing an n-alkyl chain) were approximately equal in lymphatic absorption rates, but differed markedly in the concentration of the di- and triglyceride analogues in the lymph lipids. The lymphatic absorption of triglyceride derivatives, drugs combined directly with beta-position of glycerol, was low in comparison with the monoglyceride derivatives. Compared with nicotinic acid, the alpha-monoglyceride derivative (n-alkyl chain length, Cn = 20) of nicotinic acid provided a higher AUC0-8 h value of free nicotinic acid and maintained a lower level of free fatty acids in blood.

Animals↗
PubMed1992

Contribution of interstitial diffusion in drug absorption from perfused rabbit muscle: effect of hyaluronidase on absorption.

[3H]Water and [14C]inulin were injected into perfused rabbit muscle with or without hyaluronidase (300 units/ml) and their absorption into venous effluent from muscle was determined. Hyaluronidase accelerated the absorption of both compounds but the enhancement of [14C]inulin was much larger than that for [3H]water. The pharmacokinetic analysis of venous appearance curves based on a physiological diffusion model elucidated that interstitial diffusion of [14C]inulin was remarkably increased by hyaluronidase treatment, suggesting the existence of steric hindrance for it by the polysaccharide network under normal conditions. Enhancement of [3H]water diffusion was also detected although enhancement ratio was about one-half of that of [14C]inulin. Mean time necessary for each process was calculated using the statistical moment concepts. The results suggested predominant contribution of the interstitial diffusion process and secondary and little contribution of local perfusion flow and permeation process across the capillary wall, respectively, in total absorption of [14C]inulin. Effect of hyaluronidase on transcapillary movement of [14C]inulin was studied using an in vitro diffusion experiment with cultured endothelial cell monolayer and no enhancing effect was shown on [14C]inulin transport across the cell monolayer. The contribution of the local perfusion flow, on the other hand, was shown to be almost equivalent to that of the diffusion process in the total absorption of [3H]water.

Absorption↗
PubMed1975

Thiamine absorption in the rat. ii. intestinal alkaline phosphatase activity and thiamine absorption from rat small intestine in-vitro and in-vivo.

The correlations between intestinal alkaline phosphatase (IAP) activity and thiamine absorption and glucose absorption were studied in the rat. An everted sac in-vitro technique was used in adult rats whereas in-vitro experiments were performed in young rats 10 days old. All incubation experiments were done with 14-C-labeled thiamine. The patterns of IAP activity along the small intestines differed greatly between young and adult rats but were closely paralleled by the distribution of active thiamine transport in adult rats and thiamine absorption in young rats, respectively. When IAP was specifically inhibited in adult rats by L-phenylalanine active thiamine transport in-vitro was abolished. No correlation was found between IAP activity and active transport or glucose in-vitro, nor did inhibition of the enzyme in any way affect glucose transport capacity. It is suggested that the enzyme intestinal alkalinephosphatase is involved in the process of active thiamine absorption.

Age Factors↗
PubMed1988

Absorption of 'non-absorbable' markers and an improved method for determining cholesterol absorption rates.

The determination of uptake rates for lipids across absorptive epithelia, using radiolabelled compounds has normally used non-absorbable volume markers to correct gross tissue counts for contamination by adherent mucosal fluid. There is evidence however to indicate that the macromolecules traditionally used as non-absorbable markers are in fact absorbed. This may result in an overestimate of the apparent adherent mucosal fluid with consequent errors in the calculation of lipid uptake. An in-vitro method was used to assess cholesterol absorption by human gallbladder from artificial bile, containing 3H-dextran 70,000 as a 'non-absorbable' volume marker. Both cholesterol and dextran were transported through the mucosa and appeared on the serosal side of the gallbladder. Confirmation of dextran absorption was obtained by electron microscopic examination of the gallbladder epithelium. By using the serosal appearance of dextran as a guide to the amount of absorbed (intracellular) dextran in the tissue samples, we have derived a formula to calculate tissue dextran absorption and, from the revised adherent mucosal volume, have consequently obtained more realistic estimates of tissue lipid uptake. In this study, comparison made between the previous estimate of lipid uptake compared to this new calculation, showed that the previous technique significantly underestimated true lipid uptake.

Absorption↗
PubMed1977

The absorption of phenformin and its effects on glucose and water absorption in isolated perfused rat small intestine.

The effects of phenformin on glucose and water absorption from isolated perfused rat small intestine were studied. Luminal phenformin inhibited glocose and water absorption progressively as its concentration was increased from 0-1-1-0 mg.ml-1. At 0-5 mg phenformin ml-1, inhibition increased with time of exposure to phenformin up to 15 min and thereafter remained constant. Arterial infusion of phenformin (1-0 mg-ml-1) produced less inhibition of glucose and water absorption. The site of phenformin's action appeared to be intracellular. Phenformin absorption from a luminal perfusate (0-5 mg-ml-1) was measured. Although it was rapidly absorbed (22 microgram.cm intestine-1.h-1) from the lumen, less than 2 microgram.cm-1.h-1 appeared at the serosal surface of the intestine. In subsequent phenformin-free perfusion, only 25% of the absorbed phenformin was recovered in the luminal and serosal effluents.

Animals↗
PubMed1978

GI absorption of beta-lactam antibiotics II: deviation from pH--partition hypothesis in penicillin absorption through in situ and in vitro lipoidal barriers.

The absorption of propicillin from the rat stomach and small intestine in situ was examined as a function of recirculating solution pH. The in vitro interphase transport from an aqueous buffer of various pH values to the octanol phase was also studied for several penicillins by the use of a two-phase rolling cell. The rate--pH profiles obtained from both in situ and in vitro experiments deviated significantly from the dissociation curves. The degrees of the shifts were approximately 2 pH units for the in situ intestinal absorption of propicillin and in vitro transport of propicillin and cloxacillin, approximately 1.5 pH units for the in vitro transport of penicillin V, and 0.8 pH unit for the in situ stomach absorption of propicillin. These discrepancies from the classical pH--partition hypothesis can be interpreted by the permeation through the lipoidal barrier of the undissociated species of penicillins transported through the aqueous diffusion layer adjacent to the lipoidal surface. All in situ and in vitro experiments tend to support this theory.

Animals↗
PubMed1985

Drug absorption from inhalation aerosols administered by positive-pressure ventilation. II: Effect of disodium fluorescein aerosol particle size on fluorescein absorption kinetics in the beagle dog respiratory tract.

Solid, polydispersed disodium fluorescein aerosols (MMDae = 1.1, 3.5, and 4.4 micron) were administered under the same respiratory regime, direct to the respiratory tracts of two beagle dogs by positive-pressure ventilation. Subsequent to aerosol administration, plasma fluorescein concentrations were determined after sampling from an indwelling cannula. The amount absorbed as a function of time was estimated from these and additional data collected from intravenous control experiments in the same animals. Fluorescein absorption from the respiratory tract was apparently a first-order process, the rate increasing directly with the bioavailable dose. First-order rate constants differed but appeared unrelated to aerosol particle size, possibly reflecting similarities in their regional deposition in the canine lung. The average value for the absorption half-lives in the dogs were 19.3 and 12.2 min, showing that even lipophobic solutes such as the fluorescein dianion, are absorbed extremely rapidly via the lung. In one dog, the rate constant for fluorescein absorption after intratracheal instillation of a solution of the disodium salt was within the range of those following aerosol administration. Possible explanations are discussed.

Absorption↗