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PubMed1980

Effect of metabolic acidosis in intestinal absorption of calcium and phosphorus.

To investigate the effect of metabolic acidosis on intestinal calcium (Ca) and phosphorus (P) absorption and vitamin D metabolism, metabolic balance studies and in vitro gut sac uptake of 45Ca and [32P]phosphate were performed in rats maintained on low-Ca and moderately low-P diet and fed NH4Cl for 3 or 9 days and pair-fed controls. Plasma 1,25(OH)2D concentration was measured in the rats fed NH4Cl for 9 days and their controls. Net Ca and P absorption was 87-92% in the acidotic rats and did not differ from control. Moreover, gut sac uptakes of 45Ca and [32P]phosphate were not different from control. Plasma 1,25(OH)2D was higher in the ammonium chloride-fed rats than in controls (213 +/- 44 vs. 110 +/- 12 pg/ml), and serum P was lower in the acidotic animals (4.6 +/- 0.7 vs. 7.6 +/- 0.3 mg/dl). These data indicate that metabolic acidosis does not depress the augmented intestinal absorption of calcium and phosphorus noted during their dietary deprivation nor reduce the plasma level of 1,25(OH)2D.

Acid-Base Equilibrium↗
PubMed1975

The relevance of the osmolarity of the instillation fluid to the effectiveness and toxicity of drugs given by the intraduodenal route--solvent drug influence on the intestinal absorption of drugs.

The influence of movements of fluid from the blood into the bowel lumen (solvent drag) on absorption of drugs from the intestine was studied in conscious rats with surgically implanted duodenal tubes. The drugs were given to the rats by intraduodenal instillation either in isotonic saline or in solutions of mannite having twice or three times the osmotic pressure of the blood. The instillation of hypertonic mannite solutions leads to concentration-dependent exsorption of fluid. The drugs tested were atropine and azoniaspiro compound XVII (azoniaspiro[3alpha-benziloyloxy-nortropan-8,1'-pyrrolidine]-chloride), both of which are poorly absorbed, and phenobarbital and nicotine, both of which are well absorbed. The criteria used to assess the rate of entry of the drugs into the blood stream were "efficacy" and "toxicity". In the case of atropine, azoniaspiro compound XVII and nicotine mortality rate and survival time were measured, while in the case of phenobarbital the latent period between instillation of the solution and onset of the hypnotic effect was used. As the tonicity of the solution was raised, so the concentration-dependent "efficacy" and "toxicity" declined. This meant that the latent period after instillation of phenobarbital lengthened, while after instillation of atropine, azoniaspiro compound XVII and nicotine in solutions of increasing tonicity the mortality fell and survival was prolonged. The only exception to this generalization was found when azoniaspiro compound XVII was instilled in triple strength mannite solution. The reasons for this exception were not ascertained. From the results it is concluded that "solvent drag" is an important factor in the absorption of drugs from the intestine. A stream of fluid passing into the lumen interferes with absorption, and this is reflected in the diminished "efficacy" and "toxicity" of the drug. Another factor which may influence the absorption of the drugs tested is the fall in concentration resulting from the inflow of fluid into the bowel lumen. This tends to flatten the concentration gradient between the bowel lumen and the blood and therefore delays absorption.

Animals↗
PubMed1989

Dissolution rate and in situ intestinal absorption kinetics of guanyl-cysteine.

The study of the dissolution behaviour of guanyl-cysteine is presented. The drug was assayed as a pure non-formulated product and formulated in hard gelatine capsules. Aqueous solutions buffered at different pH were used as dissolution fluids. The dissolution rate constant of the drug in this formulation was estimated. Our results show that dissolution of guanyl-cysteine occurs very rapidly. As pH of the dissolution fluid increases, the rate constant slightly decreases. The study of the absorption kinetics of guanyl-cysteine from small intestine of rats was performed with the experimental technique proposed by Doluisio. Six different concentrations of the drug were assayed for the estimation of the absorption rate constant of guanyl-cysteine under our experimental conditions. Our results show that intestinal absorption of the drug occurs as a first-order process.

Animals↗
PubMed1987

Intestinal absorption at high altitude.

Three tests of small intestinal function were performed at 3100 m and 4846 m to seek evidence of malabsorption of high altitude. Xylose tolerance did not change in 11 subjects but, in three who ascended to 5600 m, one-hour xylose levels were significantly lower. The results of an oxalate loading test did not suggest significant fat malabsorption. A direct fat absorption test using chylomicron levels after ingestion of 100 g fat showed significantly increased levels at high altitude. We conclude that there is no evidence of malabsorption up to 4846 m.

Acetazolamide↗
PubMed1998

Drug-nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine.

Fluoxetine is one of the most widely used antidepressants and nowadays it is also being used to manage obesity problems. In our laboratory we demonstrated that the drug inhibited sugar absorption (Monteiro et al. 1993). The aim of the present work was to determine the effect of fluoxetine on intestinal leucine absorption. Using a procedure of successive absorptions in vivo the drug diminished amino acid absorption by 30% (P < 0.001). Experiments in vitro in isolated jejunum also revealed a reduction in leucine uptake of 37% (P < 0.001). In both cases fluoxetine only affected mediated transport without altering diffusion. In a preparation enriched in basolateral membrane, fluoxetine inhibited the Na+,K(+)-ATPase (EC 3.6.1.37) activity (55%; P < 0.001) in a non-competitive manner with an inhibition constant (Ki) value of 0.92 mM. Leucine uptake by brush-border membrane vesicles was diminished by the drug (a reduction of 48% was observed at 30s, P < 0.001); only the apical Na(+)-dependent transport system of the amino acid was modified and the inhibition was non-competitive. Leucine uptake in the presence of lysine indicated that transporter B was involved. These results suggest that fluoxetine reduces leucine absorption by its action on the basolateral and apical membrane of the enterocyte; the nutritional status of the patients under drug treatment may be affected as neutral amino acid absorption is decreased.

Animals↗
PubMed1991

Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption.

Adult↗