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PubMed1983

Impaired intestinal absorption of vitamin D3 in azotemic rats.

Changes in vitamin D metabolism and their effect on calcium and bone metabolism in uremia have been extensively studied. However, the possible effect of uremia on intestinal absorption of vitamin D has not been investigated. We determined the rate of intestinal absorption of vitamin D3 in uremic and normal rats using a well-defined in vivo perfusion technique under identical experimental conditions. The rate of jejunal absorption of vitamin D3 in uremic animals (5.09 +/- 1.87 pmol/100 cm/h) was significantly less (p less than 0.001) than that found in the control animals (11.5 +/- 1.6 pmol/100 cm/h). While the underlying mechanism(s) of the observed reduction in vitamin D absorption in uremia is not known, its recognition adds another dimension to the previously recognized abnormalities of vitamin D metabolism in uremia.

Animals↗
PubMed1993

Influence of anesthetic regimens on intestinal absorption in rats.

We compared the influence of anesthetic regimens using urethane (U), pentobarbital (P), ether (E), and ketamine/midazolam (K) on the intestinal absorption of several probes using a single-pass perfusion technique in rats. The selected probes were D-glucose (1 mM) for the resistance of the unstirred water layer (UWL), D-glucose (100 mM) for the capacity of carrier-mediated D-glucose transport, L-glucose, and urea for membrane-limited passive transport, and tritiated water (3H2O) for blood flow at the absorption site. The absorbed fraction of D-glucose (1 mM) was the smallest for U and the largest for P, suggesting that the resistance of UWL is the largest for U and the smallest for P. The absorbed fraction of D-glucose (100 mM) was the largest for P (U = E = K < P), suggesting a higher capacity of carrier-mediated D-glucose transport for P. The absorbed fraction of urea was similar for all anesthetics, while that of L-glucose was the smallest for K (U = P = E > K). Although the results for these two markers of membrane-limited passive transport were inconsistent, the passive permeability of the intestinal membrane may be lower when treating with K. The intestinal absorptions of D-glucose (1 and 100 mM), L-glucose, and urea were, in general, lower with any of the anesthetics than under nonanesthesia (N), suggesting increased resistance of UWL and decreased intestinal membrane permeability by carrier-mediated and passive transport under anesthesia. The only exception was the absorption of D-glucose (100 mM) under P, which was comparable to that under N.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1977

[Decrease of intestinal absorption of 47-calcium in chronic alcoholism].

Intestinal 47-calcium absorption has been studied in 34 chronic alcoholics, 17 of whom were cirrhotics (group A) and 17 non-cirrhotics (group B). These patients were compared with 44 normal subjects (group C). In group C, the 47Ca 2 h plasma % of the dose showed a significant negative correlation to the total body weight (p less than 0.001) and a positive correlation with the serum albumin (p less than 0.05). The mean intestinal absorption of 47Ca expressed as 2 h plasma % of the dose multiplied by total body weight was 131 +/- SD 52 in group A and 136 +/- SD 71 in group B. These two means are significantly low (p less than 0.001 and p less than 0.002 respectively) in relation to that found in group C (168 +/- SD 32). These results suggest that intestinal calcium absorption is diminished in chronic alcoholism even in the absence of hepatic cirrhosis.

Alcoholism↗
PubMedDate not supplied

Functional role of P-glycoprotein in limiting intestinal absorption of drugs: contribution of passive permeability to P-glycoprotein mediated efflux transport.

The aim of the present study is to evaluate the quantitative contribution of passive permeability to P-glycoprotein-mediated (P-gp-mediated) efflux and the functional activity of P-gp in determining intestinal absorption of drugs, and demonstrate the relationship between efflux parameters and intestinal permeability. MDRI-MDCKII cell monolayer permeability, human intestinal absorption (HIA), and solubility data were systematically collected from the literature. Drugs were classified as a total of 63 P-gp substrates (P-gpS) and 73 nonsubstrates (NS) on the basis of efflux ratio or calcein AM inhibition and ATPase activity assays. Efflux parameters, efflux ratio (ER) and absorption quotient (AQ), were correlated to the monolayer permeability. MDRI-MDCKII cell monolayer permeability characteristics were found to be distinctly different between P-gpS and NS datasets. The ER for P-gpS was found to increase with absorptive permeability until 20 nm.s(-1), but reduced for P-gpS with high absorptive permeability. The AQ showed a linear inverse relationship with absorptive permeability. Overall, efflux parameters, ER and AQ, indicated that the transport of P-gpS with moderate passive permeability is highly attenuated by P-gp, while passive permeability overrules the P-gp-mediated efflux for high-permeability molecules. Most of the P-gpS were found towards the upper limits of molecular weight (>500) and calculated total polar surface area (>75 A(2)). This dataset indicated that unfavorable chemical features of P-gpS limit passive permeability and thus are more susceptible to P-gp-mediated efflux. In conclusion, passive permeability versus P-gp-mediated efflux determines intestinal permeability of P-gpS, where P-gp limits absorption of only moderately permeable compounds. Thus, integrating these factors with drug characteristics of the Biopharmaceutics Classification System (BCS) class better predicts the functional role of P-gp in limiting intestinal drug absorption.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1995

Method to estimate the rate and extent of intestinal absorption in conscious rats using an absorption probe and portal blood sampling.

PURPOSE: A variety of methods exist which determine the rate and extent of intestinal absorption. The method described here employs an internal absorption reference probe and portal blood sampling in unanesthetized rat. METHODS: Theophylline and tritiated water were selected as absorption reference probes since they are quantitatively absorbed in conscious rat. The fraction of an intestinal dose which reaches portal blood was determined from the resulting portal-systemic blood concentration gradients of the drug relative to the absorption probe. The absorption probes provide a means to calculate the drug mass reaching portal blood without the need of measuring the portal blood flow rate. The technique was evaluated with verapamil and a well-absorbed 5-lipoxygenase inhibitor, A-79035. RESULTS: The fraction of an intrajejunal dose of A-79035 reaching the portal vein (FG) was 0.86 using theophylline as the absorption probe. Verapamil, which is susceptible to extensive hepatic first-pass elimination, was completely absorbed (FG = 0.98) within 1 hour, but was only 21.4% bioavailable. Absorption rate constants, estimated from initial appearance rates in portal blood, were used to monitor factors that affect drug absorption. For example, with a dose solution containing 30% PEG-400, the absorption rate constants of theophylline and A-79035 were significantly reduced. Anesthesia reduced the absorption rate constant for theophylline in rats by 40% compared to conscious animals. CONCLUSIONS: The technique detailed here allows reliable, direct measurement of intestinal absorption which may assist in characterizing oral dosing for novel therapeutic agents.

Animals↗
PubMed1975

Inhibition of intestinal absorption of phenylalanine by phenylalaninol.

Plasma phenylalanine and tyrosine levels in rats which had been orally administered L-phenylalaninol and L-phenylalanine were determined. Since these amino acid levels in rats administered L-phenylalanine solution containing L-phenylalaninol were significantly lower than those in rats administered L-phenylalanine alone. L-phenylalaninol appears to inhibit the intestinal absorption of L-phenylalanine. This effect was more potent than that of cycloleucine. L-phenylalaninol inhibited the phenylalanine transport of everted sacs. The Km value of L-phenylalanine was 3.44 X 10(-3) M and the Ki value of L-phenylalaninol was 7.69 M 10(-3) M from Lineweaver-Burk plots. From these two curves, it appeared that L-phenylalaninol may competitively inhibit the intestinal transport of L-phenylalanine. The effects of L-phenylalanine, L-phenylalaninol and cycloleucine on the urinary excretions of Na+ and K+ in rats were also examined. Potassium excretion which increased on oral administration of L-phenylalanine, was suppressed by the administration of L-phenylalaninol but not administration of cycloleucine. L-phenylalaninol alone enhanced Na+ excretion in urine. These results confirmed that L-phenylalaninol shows inhibitory effects as potent as those of cycloleucine on the intestinal absorption of L-phenylalanine.

Animals↗
PubMed1978

Validation of the use of a tube with a proximal occlusive balloon for measurement of intestinal absorption in man.

Because of its simplicity, a tube with a proximal occlusive balloon is widely used to measure segmental intestinal absorption in man. Yet, the possibility that the presence of an inflated balloon might alter the absorptive capacity of the underlying segment of intestine has never been tested. In the present work the jejunal absorption of water and ions has been measured in 13 healthy subjects with the proximally occlusive tube and with the triple lumen nonocclusive method; precautions were taken to achieve similar flow rate and ionic composition of the fluid entering the test segment with both techniques in each subject. Under these conditions net water and ion movements measured by the two methods were identical. This finding validates the use of the proximal occlusive tube to measure intestinal absorption in man.

Electrolytes↗
PubMed1992

Evaluation of the mass balance assumption with respect to the two-resistance model of intestinal absorption by using in situ single-pass intestinal perfusion of theophylline in rats.

Methods of analyzing drug absorption data from rat intestinal-perfusion experiments are discussed in terms of mass-transfer resistances, or reciprocal permeabilities, and mass balances. Typically, a two-resistance model is used to determine the dimensionless effective permeability (P*eff) by measuring the disappearance of drug from the perfusing solution. Unstated assumptions in two-resistance models are (1) the portal blood is under sink conditions and (2) complete transfer of drug occurs from the intestinal perfusate to the portal vein. The assumption of sink conditions is generally acceptable, because the drug concentration in portal blood is approximately two orders of magnitude less than in the perfusate. Single-pass intestinal-perfusion experiments were performed on rats with theophylline as a model compound. The drug mass leaving the intestinal perfusate was substantially less than the drug mass appearing in the portal plasma; that is, the assumption of complete transfer did not hold for theophylline in this experimental system. These data indicate that models based on the two-resistance theory can lead to overestimation of P*eff by the ratio of the drug mass leaving the perfusate to the drug mass appearing in the plasma. For compounds for which the assumption of complete transfer does not hold, a more accurate estimate of P*eff may be determined by dividing the value derived from perfusate data by the mass balance ratio (i.e., the drug mass leaving the perfusate divided by the drug mass appearing in the plasma).

Animals↗
PubMed1997

Influence of dietary fat on the intestinal absorption of lipophilic compounds in goldfish (Carassius auratus).

Dietary uptake of a mixture of pp'DDT and four chlorobenzenes from diets with different lipid contents was measured in goldfish (Carassius auratus) in order to investigate the mechanism of intestinal absorption of organic compounds. The results of the experiments suggest that intestinal absorption is basically controlled by chemical diffusion rather than lipid coassimilation. The extent of dietary uptake as indicated by biomagnification factor was strongly correlated with the chemical log Kow, indicating that uptake of the chemicals from the gastrointestinal fluid is similar to the uptake from other aqueous environments and lipid content of the food in the range used in these experiments (2.9-10.9%) could not influence the uptake of lipophilic chemicals.

Animals↗
PubMed1995

Regiospecific intestinal absorption of the HIV protease inhibitor L-735,524 in beagle dogs.

PURPOSE: To evaluate regional intestinal absorption and the feasibility of sustained release dosage form development for an HIV protease inhibitor, L-735,524, METHODS: L-735,524 free base or sulfate salt was administered orally as suspension, solution or in solid dosage forms to fasted or fed Beagle dogs. Delayed-release dosage forms with "slow" or "fast" in vitro dissolution rates were evaluated in vivo to assess plasma concentration profiles. In addition, drug was administered directly into the jejunum or colon of animals, and drug concentrations determined in portal circulation to characterize absorption from these sites. RESULTS: L-735,524 sulfate was well absorbed orally form a solution or capsule formulation if fasted animals' stomachs were preacidified with citric acid solution. A free base suspension, delivered in divided doses to fed animals, was also well absorbed. Prototype extended release dosage forms of L-735,524 produced a reduction in peak plasma levels but failed to prolong absorption and extend plasma concentrations compared to an immediate release capsule. Administration of L-735,524 sulfate solution (pH < 3) as bolus solution or by infusion into the jejunum resulted in rapid but incomplete absorption compared to oral gavage. The free base suspension (pH 6.5) delivered into jejunal or colonic regions did not produce measurable systemic plasma concentrations. CONCLUSIONS: Extended release formulations did not prolong absorption of L-735,524 in dogs. Optimal L-735,524 absorption was dependent on solubility in an acidic environment in the duodenum.

Administration, Oral↗
PubMed1970

Brush border development in the intestinal absorptive cells of Xenopus during metamorphosis.

The differentiation of the brush border which makes up the apical free surface of intestinal absorptive cells has been studied by electron microscopy. Specimens of Xenopus small intestine were fixed at various stages during metamorphosis, the time when a new intestinal epithelium forms. The interpretation of details described herein emphasizes the role of "surface-forming" vesicles. These vesicles are thought to provide membrane both for the initial expansion of the apical surface and for the later elongation of the microvilli. The latter are believed to be "molded" around filamentous cores that appear early in differentiation. The cores are attached to the apical membrane and extend vertically into the supranuclear cytoplasm. This interpretation rests chiefly on (a) the resemblance, both in morphology and in staining properties with colloidal thorium, between the membrane that limits the vesicles and that which limits the microvilli and (b) the distribution and time of appearance of the vesicles with respect to development of the microvilli. According to this view, the specific properties of surface membrane reside in preformed units that arise within the supranuclear cytoplasm. This morphogenetic process probably involves participation of the Golgi region as the site where the complex macromolecular architecture of the cell surface is assembled.

Animals↗
PubMed2000

Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study.

BACKGROUND: High dose growth hormone, glutamine, and a high carbohydrate diet may improve intestinal function in short bowel patients. AIMS: To investigate if growth hormone with glutamine and no change in diet improved intestinal function. PATIENTS AND METHODS: Eight short bowel patients were randomised in a double blind crossover study between placebo and growth hormone (mean 0.12 mg/kg/day) with oral (mean 28 g/day) and parenteral glutamine (mean 5.2 g/day) for 28 days. Balance studies were performed at baseline and five days after placebo and treatment were terminated. Dietary energy, carbohydrate, and fat were maintained as usual. RESULTS: Growth hormone with glutamine did not improve intestinal absorption of energy (baseline, placebo, treatment, mean: 46%, 48%, 46% of oral intake, respectively), carbohydrate (71%, 70%, 71%), fat (20%, 15%, 18%), nitrogen (27%, 18%, 19%), wet weight (37%, 39%, 31%), sodium (-16%, -16%, -36%), potassium (43%, 47%, 33%), calcium (-16%, -16%, -15%) or magnesium (-3%, 4%, 2%) compared with placebo or baseline (p>0.05) five days after treatment was terminated. All patients experienced adverse effects. CONCLUSIONS: Combined high dose growth hormone and glutamine administered for four weeks did not improve intestinal absorption five days after treatment was terminated in short bowel patients on their usual diet.

Adult↗
PubMed1978

[Intestinal absorption in the elderly (author's transl)].

The extent of intestinal absorption and malabsorption may be exactly stated by means of the method "generalized absorption". According to first-hand examinations an alteration of absorbing kinetics of D-xylose dependent on age could have been demonstrated. The velocity of absorption decreases in the elderly and the general absorbing process are prolonged. The extent of absorption restriction in the elderly are under physiological circumstances without clinical value. The health elder man disposes of the same power for a complete absorption of an offered substrate like the younger one. An increasing of cases with a malabsorption in the age may be explained by a increased multmorbidity in the elderly.

Adolescent↗
PubMed1988

In vivo model for ciclosporin intestinal absorption in lipid vehicles.

The influence of lipid vehicles on the intestinal absorption of Ciclosporin was studied in vivo. The model takes into account the effect of the intestinal lipid digestion on the absorption after intraduodenal administration of [3H]Ciclosporin in olive oil or middle-chain triglyceride (MCT) to the bile duct-cannulated rat. Digested vehicles significantly promoted the absorption compared to nondigested vehicles. In the nondigested state, olive oil was a significantly better vehicle than MCT, whereas the difference between both lipids was only a trend in the digested state. Further studies with variants of this in vivo model should determine the influence of abnormalities of fat digestion and absorption on the pharmacokinetics and pharmacodynamics of a drug with a low therapeutical index.

Animals↗
PubMed1983

Effects of steroids and sex reversal on intestinal absorption of L-[14C]leucine in vivo, in rainbow trout, Salmo gairdneri.

The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-[14C]leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of 14C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of 14C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function.

Animals↗
PubMed1999

Effects of ethanol on intestinal absorption of drugs: in situ studies with ciprofloxacin analogs in acute and chronic alcohol-fed rats.

BACKGROUND: Previous work from our laboratory on the effect, in rats, of chronic ethanol intake on the intestinal absorption of ciprofloxacin analogs suggested an increased polarity of the lipoidal membrane constituents without effects on the aqueous environment. The aim of the present study was to investigate the influence of acute ethanol intake on the absorption of the same series of compounds. METHODS: The effects of in situ ethanol exposure on intestinal absorption were determined in rats fed either a standard liquid diet or a 5% (w/v) ethanol-containing liquid diet. Acute intestinal exposure to 5% (w/v) ethanol was performed in situ in each feeding group. The biophysical absorption model was used to establish correlations between the actual absorption rate constants, and the lipophilicity indexes, for each group of rats. RESULTS: Acute exposure to ethanol produces an increase only in the absorption of hydrophilic homologs in both control and chronic ethanol fed groups. This suggests the absence of homeoviscous adaptation of the intestinal membrane. The biophysical model used allows us to discriminate between the effects of acute and chronic ethanol treatment on the intestinal membrane. CONCLUSIONS: These results suggest that in contrast to previous reports chronic ethanol treatment increases membrane polarity and acute alcohol intake appears to modify membrane fluidity.

Animals↗
PubMed1980

Effect to cholecalciferol and 1,25-Dihydroxycholecalciferol on the intestinal absorption of zinc in the chick.

The effect of cholecalciferol on the intestinal absorption of 65Zn was assessed in zinc-deficient and zinc-replete rachitic chicks, using the in situ ligated loop techniques. Cholecalciferol did not significantly affect 65Zn absorption in either group, although the synthesis of the intestinal calcium-binding protein (CaBP) in both groups was similar. In an analogous study, 1,25-dihydroxycholecalciferol increased 47Ca absorption and induced the synthesis of CaBP but exerted on effect on 65Zn absorption in zinc-deficient rachitic chicks. When fed a diet adequate in cholecalciferol, more CaBP was present in the intestine of the zinc-adequate group than in the zinc-deficient group, possibly due to the greater rate of growth and therefore the greater need for calcium by the former group. These results suggest that cholecalciferol and its most active metabolite do not directly affect zinc absorption and, by inference, that the vitamin D-dependent transport mechanism is not involved in zinc homeostasis, or in the interaction between calcium and zinc.

Animals↗
PubMed1979

Intestinal absorption of bile salts: immature development in the neonate.

The intestinal absorption of sodium taurocholate was studied in fetuses, neonates, infants, children, and adults. Absorption rates were measured in vitro in everted rings of jejunum and ileum. Mucosal accumulation of 3H-taurocholate against a concentration gradient was consistently demonstrated in rings of ileum from adults, children, and infants older than 8 months, whereas fetal and neonatal ileal mucosal concentrations were not significantly above those in the incubation medium after exposure of the mucosa to 0.003, 0.03, and 0.3 mM taurocholate. There were no significant differences in mucosal uptake of taurocholate by perinatal jejunal and ileal rings. Incubations of mucosa from older infants, children, and adults in 0.3 mM taurocholate exhibited saturation phenomena. It is concluded that the ileal mechanism for active transport of taurocholate is undeveloped in the fetus and newborn infant. It is probable that the enterohepatic circulation of bile salt during the perinatal period is limited to that fraction of bile salt absorbed passively. The results suggest that losses of bile salt from the immature intestine may contribute to the steatorrhea and so-called diarrhea of newborn infants.

Aged↗