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Estimation of drug absorption rates using a deconvolution method with nonequal sampling times.

A method affording direct estimation of the drug absorption rate from blood level data using arbitrary time intervals has been derived based on the staircase input principle. In the derivation, the drug was assumed to follow linear kinetics where the plasma concentration of the drug after an impulse input is expressed by a multiexponential function. Drug absorption was assumed to occur at a constant rate during each subsequent sampling interval. The absorption rate profiles obtained by the method using several numerical examples were expressed as a set of rectangular pulses. Divergence in the profiles reflected blood sampling measurement errors rather than errors due to the deconvolution. Smoothing of the rate profiles by calculating the mean of the absorption rates between adjacent time intervals gave realistic results. Absorption rate profiles for theophylline obtained by the method using published data gave information on the initiation and termination of the absorption as well as the extent of absorption from the dosage form.

Humans↗

Effect of diester and diether phosphatidylcholine on intestinal absorption of neutral and acidic sterols.

The effects of nondigestible diether phosphatidylcholine on intestinal absorption of cholesterol and dihydroxy and trihydroxy conjugated bile salts were studied in bile fistula rats using radioactive substrates. No inhibition of absorption of either dihydroxy or trihydroxy bile salts was observed. Nondigestible phospholipid did, however, significantly inhibit cholesterol absorption. Under control conditions with natural phosphatidylcholine in the intestinal perfusate, absorption of cholesterol was significantly greater when infused with taurocholate (TC) as compared to results obtained after infusion with taurochenodeoxycholate (TCD). Studies were repeated using radioactive rat liver phosphatidylcholine to determine whether the observed decrease in cholesterol absorption could be correlated with a decrease in digestion and absorption of rat liver phosphatidylcholine. No evidence was found for decreased absorption of this phospholipid when given with TCD. It is concluded that less cholesterol is absorbed in the presence of TCD as compared to TC, but the mechanism for this remains unexplained.

Animals↗

Absorption of different amino acids by an intestinal preparation from normal rats and from rats exposed to supralethal X-irradiation.

Absorption of different amino acids [lysine, alpha-amino isobutyrate (AIB), methionine, alanine, glycine] was studied in an intestinal in vivo preparation from normal and X-irradiated rats (1 and 3 days after 2000 R). Absorption of amino acids under loading and in presence of other amino acids was also followed. Lysine and AIB absorption follow a saturation kinetics with a maximal velocity of 35 and 85.6 micronmoles/min and a Kt of 10 and 67 micronmoles for lysine and AIB respectively. Interference in absorption exists not only between amino acids of the same class, but also by lysine on neutral amino acids. One day after irradiation, absorption is normal or even enhanced, although active transport appears impaired as indicated by the increase in Kt. Three days after exposure absorption, particularly the active one, is severely depressed. This is indicated by the low Vm and high Kt as well as by the fact that loading has little influence on absorption.

Alanine↗

Loss of absorptive capacity for sodium chloride as a cause of diarrhea following partial ileal and right colon resection.

Previous studies have emphasized the role of bile acid and fat malabsorption as the cause of the diarrhea that may follow ileal and right colon resection; unabsorbed bile acids and fat are believed to reduce sodium chloride and water absorption in the remaining colon. In this paper we report studies in eight patients with severe postresection diarrhea, in search of a more basic defect in sodium chloride absorption, ie, a loss of sodium chloride absorptive capacity as a direct consequence of resection of sodium chloride absorption sites. First, we determined whether or not diarrhea persisted during a 48-hr fast; in all patients diarrhea and large fecal electrolyte losses continued during a fast. Second, we measured sodium chloride and water absorption rates during total gut perfusion with a balanced electrolyte solution; compared to normal controls, the patients absorbed 23-31% less water, sodium, and chloride. In three patients who could be studied further, the absorptive defect was markedly accentuated when the perfusing solution was such that sodium chloride absorption had to take place against a concentration gradient. These observations indicate that postresection diarrhea patients have a reduced capacity to absorb sodium chloride, particularly when there is a concentration gradient between lumen and plasma. Although all of these patients had malabsorption of radiolabeled taurocholic acid, there was only a modest and statistically insignificant reduction in daily stool weight during treatment with large doses of cholestyramine, suggesting that bile acid malabsorption was not responsible for a major part of their diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intestinal calcium absorption from different calcium preparations: influence of anion and solubility.

Not only is the calcium content of a preparation significant for providing adequate calcium supplementation for the prophylaxis and therapy of osteoporosis, but also its bioavailability is of essential importance. In the present study, the bioavailability of calcium citrate and calcium lactogluconate/carbonate from a therapeutic dose (= 500 mg Ca2+) was compared in men aged between 45 and 60 years on an intra-individual basis. Calcium citrate was administered both as a solution and as a suspension to 18 healthy volunteers. Using a double-isotope method, the intestinal absorption from the three preparations was determined in randomized order at intervals of 2-4 weeks. The stable isotope 44Ca (20 mg), in highly enriched form, was added in each case to the ready-to-drink solutions and, at the same time, a sterile and pyrogen-free solution containing 5 mg of the stable isotope 42Ca was injected intravenously. The intestinal calcium absorption was then determined after 24 h on the basis of the ratio of the two isotopes in the plasma. There was a significantly higher absorption of 29% from the citrate solution than from the lactogluconate/carbonate solution (25%). Absorption from the citrate suspension was similar to that from the lactogluconate/carbonate solution. While no correlation was found between the measured values for calcium absorption from the three preparations and the plasma concentration of 1,25-dihydroxycholecalciferol, significant inverse correlations with the basal parathyroid hormone concentration were observed for the citrate and lactogluconate/ carbonate solution. The results of this study show that quantitative data on intestinal calcium absorption can be obtained without employing radioactive isotopes in humans. Moreover, they show that calcium absorption is not determined only by the solubility and the degree of ionization of the calcium salt administered, but rather that it is of a complex nature.

Biological Availability↗

Calcium absorption in the rat as influenced by highly selective vagotomy with special regard to endogenous gastrin.

The effect of HSV (controls: sham), which induces hypergastrinemia, on duodenal Ca absorption was studied in "intact", TPTX, PTX, and TX rats. Ca absorption was estimated by an in vivo loop technique. As this technique increased serum gastrin by the duodenal Ca load, gastrin was also measured in rats not subjected to evaluation of Ca absorption. Following vagotomy gastrin rose significantly in "intact" as well as in TPTX, PTX, and TX rats. Further, intraduodenal Ca increased gastrin both after sham and vagotomy. However, gastrin in vagotomized rats was significantly higher than in sham rats, too. Although duodenal Ca absorption was not altered by vagotomy in "intact" and in TX rats, it was significantly lowered in vagotomized TPTX and PTX rats. Pretreatment of TPTX rats by pentagastrin for 10 days or immediately preceding experiments did not change Ca absorption. In addition, serum parathyroid hormone was unchanged by vagotomy in "intact" rats as compared to sham controls. We conclude that (1) vagotomy does not influence the rate of duodenal Ca absorption in "intact" rats, (2) Ca absorption is lower after vagotomy only in the absence of parathyroid glands, and (3) this vagotomy effect is not mimicked by exogenous pentagastrin and therefore appears unrelated to endogenous postvagotomy gastrinemia.

Animals↗

Meal-stimulated canine jejunal ionic absorption. Influence of mucosal neural blockade.

The oral ingestion of a meal or the delivery of nutrients directly to the stomach or duodenum stimulates water and ion absorption from the proximal jejunal lumen. To further investigate this phenomenon, this study tested two hypotheses: (1) direct jejunal nutrient delivery stimulates jejunal absorption, and (2) the signal for jejunal absorption requires intact enteric neurotransmission and will therefore be altered by mucosal neural blockade with the local anesthetic bupivacaine. Intestinal absorption studies (N = 52) were performed on eight dogs with 25-cm jejunal Thiry-Vella fistulas (TVF) and feeding jejunostomies. Luminal perfusion with [14C]PEG was used to calculate TVF absorption of H2O, Na+, and Cl-. Six groups were randomly studied over 4 hr. Each group incorporated a basal hour, a TVF or jejunostomy treatment hour, and an oral (groups 1 and 3) or a jejunal (groups 4 and 6) meal stimulus. The oral and jejunal meals were isocaloric and of identical composition. Groups 1-3 had saline (as a control) or 0.75% bupivacaine applied to the lumen of the TVF. Groups 5 and 6 had 0.75% bupivacaine application to the feeding jejunostomy. Both the oral and the jejunal meal stimuli resulted in a significant proabsorptive response in the TVF. TVF bupivacaine reduced basal absorption but did not diminish the meal-induced proabsorptive response. Treatment of the jejunostomy with bupivacaine caused no change in basal or postmeal absorption in the TVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Butyrate absorption and lactate secretion in ulcerative colitis.

PURPOSE: Fecal electrolytes and organic anion concentrations are altered in ulcerative colitis, presumably reflecting changes in colon epithelial transport. Information of mucosal absorption of butyrate in active ulcerative proctosigmoiditis is not available. METHODS: Dialysis bags containing 70 mmol/liter of butyrate in an isotonic electrolyte solution were placed in the rectum for 30 minutes. Net absorption or secretion rates of butyrate, lactate, and electrolytes were determined in the rectum of 12 patients with active ulcerative colitis (UC) and in 10 patients with quiescent UC and then compared with 10 healthy controls. RESULTS: Net flux rates demonstrated a considerable absorption of butyrate in patients with active inflammation of 7.5 +/- 0.4 mumol/cm2/h and quiescent colitis of 6.6 +/- 0.4 mumol/cm2/h, equal to absorption in healthy controls of 6.3 +/- 0.5 mumol/cm2/h, P = 0.12. Despite normal butyrate absorption, sodium absorption was compromised in active ulcerative colitis (11.5 +/- 1.4 mumol/cm2/h) compared with quiescent (15.4 +/- 1.0 mumol/cm2/h) and controls (18.7 +/- 0.8 mumol/cm2/h) (P = 0.0006). Mucosal secretion of L-lactate was minimal in both healthy controls and quiescent UC but significantly increased in patients with proctosigmoiditis (0.2 +/- 0.1 mumol/cm2/h, 0.2 +/- 0.1 mumol/cm2/h vs. 0.9 +/- 0.2 mumol/cm2/h; P = 0.0001). Appearance of D-lactate was negligible in all three groups. CONCLUSIONS: This study demonstrates that rectal butyrate absorption is normal in UC, and it follows that butyrate supplied in enemas can be expected to be absorbed. The inflamed colonic mucosa secretes L-lactate, and the increased fecal lactate concentrations can be explained by mucosal origin of lactate.

Adult↗

D-xylose hydrogen breath tests compared to absorption kinetics in human patients with and without malabsorption.

The D-xylose breath H2 test may be useful in characterizing intestinal absorptive function. Our aim was to determine whether breath H2 following D-xylose administration reflects the extent to which the D-xylose is absorbed by comparing it to a kinetic model of D-xylose absorption. Twenty-five subjects were studied. They ingested 15 g D-xylose on the first day and 25 g D-xylose on the third day. On the second day they received 10 g intravenous D-xylose along with 15 g oral lactulose. Multiple serum and urine samples were obtained for D-xylose content to calculate its rate constants and extent of absorption by multicompartmental analysis. Breath H2 determinations were obtained every 15 min for 3 hr following the 15 g D-xylose and lactulose ingestion. Peak breath H2 concentration correlated with extent of absorption (r = -0.787, P < 0.001), K0, the rate constant for nonabsorptive loss (r = 0.744, P < 0.001), and 5-hr urine content (r = -0.705, P < 0.001). Area under the breath H2 curve also correlated with these parameters: extent of absorption (r = -0.770, P < 0.001), K0 (r = 0.662, P < 0.001), 5-hr urine content (r = -0.629, P < 0.012). Peak D-xylose breath H2 to peak lactulose breath H2 showed no correlation with extent of absorption. The extent of absorption was higher with the 15-g dose than the 25-g dose in all patients tested (P < 0.01). (ABSTRACT TRANCATED AT 250 WORDS)

Administration, Oral↗

Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat.

The lumen of the small intestine in anesthetized rats was recirculated with 50 ml perfusion fluid containing normal salts, 25 mM glucose and low concentrations of hydrophilic solutes ranging in size from creatinine (mol wt 113) to Inulin (mol wt 5500). Ferrocyanide, a nontoxic, quadrupally charged anion was not absorbed; it could therefore be used as an osmotically active solute with reflection coefficient of 1.0 to adjust rates of fluid absorption, Jv, and to measure the coefficient of osmotic flow, Lp. The clearances from the perfusion fluid of all other test solutes were approximately proportional to Jv. From Lp and rates of clearances as a function of Jv and molecular size we estimate (a) the fraction of fluid absorption which passes paracellularly (approx. 50%), (b) coefficients of solvent drag of various solutes within intercellular junctions, (c) the equivalent pore radius of intercellular junctions (50 A) and their cross sectional area per unit path length (4.3 cm per cm length of intestine). Glucose absorption also varied as a function of Jv. From this relationship and the clearances of inert markers we calculate the rate of active transport of glucose, the amount of glucose carried paracellularly by solvent drag or back-diffusion at any given Jv and luminal glucose concentration and the concentration of glucose in the absorbate. The results indicate that solvent drag through paracellular channels is the principal route for intestinal transport of glucose or amino acids at physiological rates of fluid absorption and concentration. In the absence of luminal glucose the rate of fluid absorption and the clearances of all inert hydrophilic solutes were greatly reduced. It is proposed that Na-coupled transport of organic solutes from lumen to intercellular spaces provides the principal osmotic force for fluid absorption and triggers widening of intercellular junctions, thus promoting bulk absorption of nutrients by solvent drag. Further evidence for regulation of channel width is provided in accompanying papers on changes in electrical impedance and ultrastructure of junctions during Na-coupled solute transport.

Animals↗

Role of brush border Na+/H+ exchange in canine ileal absorption.

Na+/H+ exchanger isoforms have been identified in mammalian intestinal enterocytes and cloned: NHE1 on the basolateral membrane regulating intracellular pH; and NHE2 and NHE3 on the brush border serving transcellular absorption in Na+. NHE1 and NHE2 are much more sensitive to inhibition by amiloride than NHE3, their in vitro IC50s for amiloride being 1 microM, 1 microM and 39 microM, respectively. This study tested the hypothesis that the brush border NHE3 isoform plays the predominant role in basal and meal-stimulated ileal absorption. Absorption studies (N = 72) were performed in dogs with 25-cm ileal Thiry-Vella fistulae. Six groups were studied over 4 hr. Perfusion with [14C]PEG and 140 mM Na+ was used to calculate absorption of water, ions, and glucose. Luminal amiloride was administered from the second to the fourth hours at doses of 20 microM in groups 3 and 4 to inhibit NHE1 and NHE2, and 1mM in groups 5 and 6 to also inhibit NHE3. A 480-kcal canine meal was ingested after the second hour in groups, 2, 4, and 6. Meal ingestion was followed by significant increases in water and electrolyte absorption. Amiloride (1 mM) caused significant reductions in basal and meal-stimulated ileal absorption, while the 20 microM dose had no effect on either. These data are consistent with the hypothesis that NHE3, but not NHE2, is involved in basal and meal-stimulated ileal water and Na+ absorption.

Amiloride↗

Oral absorption of CGS-20625, an insoluble drug, in dogs and man.

Oral bioavailability of highly water-insoluble drugs is often quite limited and variable, requiring the development of improved formulations. Animal models are an essential aspect of the design and testing of such formulations designed to improve absorption in man. The present report compares the absorption of CGS-20625, an insoluble drug, in dog and man after oral administration of the drug as a powder, a solid dispersion capsule, and after gastric and duodenal administration in PEG 400 solution. CGS-20625 powder (20 mg) given orally exhibited slow, delayed absorption in both dog and man, with a Cmax of 0.26 +/- 0.07 microgram/ml at Tmax of 3 hr in dog, and 0.01 +/- 0.004 microgram/ml at 2 hr in man. Administration of CGS-20625 in PEG 400 solution improved absorption in dog and man, with a Cmax of 1.2 +/- 0.10 microgram/ml at Tmax of 0.25 hr in dog, and a Cmax of 0.10 +/- 0.04 microgram/ml at 0.5 hr in man. Tmax after administration of the hard gelatin capsule formulation was 0.9 and 1.0 hr in dog and man, with Cmax of 0.89 +/- 0.16 and 0.052 +/- 0.014 microgram/ml, respectively. Absolute bioavailability of CGS-20625 powder in the dog was 0.67 +/- 0.21, whereas the bioavailabilities of the powder and the capsule relative to the PEG 400 solution were 0.84 and 1.1, respectively, in dog, and 0.41 and 0.85 respectively, in man. No significant benefits of duodenal administration were observed. Plasma levels were approximately 10-fold greater and oral clearance was approximately 5-fold less in the dog than in man. Furthermore, pharmacokinetic data were less variable and relative bioavailability was greater in dogs than in humans. Physiological factors in the gastrointestinal tract or greater first-pass metabolism in man may account for these species differences. The relative rate and extent of CGS-20625 absorption were similar between dog and man, in the order of powder < capsule < PEG 400 solution. In addition, in vivo absorption rates in both species reflect in vitro dissolution differences between the powder and the capsule. These data strongly support the use of the dog as a model for developing improved formulations of CGS-20625. Further investigation of the dog as a model to evaluate insoluble drug absorption is warranted.

Absorption↗

We may not measure the correct intestinal wall permeability coefficient of drugs: alternative absorptive clearance concept.

It is shown that the conventional method (based on the thin-wall membrane theory) of studying the rate of disappearance or absorption from the lumen alone may not yield the correct intestinal wall (membrane) permeability coefficient of drugs. Potential reasons for causing this problem such as first-pass metabolism and accumulation of drugs in gut wall or tissue as well as back diffusion of drugs from the gut tissue to the lumen (i.e., a part of exsorption phenomenon) and potential major transport barriers across the protoplasm, basal membrane, and basement membrane are discussed. Contrary to the conventional concept, basal and basement membranes should also be considered major barriers for absorption into the blood for compounds with low intestinal permeability, and the protoplasm or cytoplasma should also be considered a major absorption barrier for compounds with high intestinal permeability. Strictly speaking, the conventional experimental method cannot be considered a bona fide method for studying drug permeability that deals with the movement of drug molecules from one side to the other side of a membrane, cell, medium, or device. The wall permeability coefficient thus obtained may therefore not represent the true wall permeability coefficient. "Intestinal absorptive clearance per unit gross surface area" is advocated as the best alternative term because it should more accurately reflect the true meaning of an experimental result for any compounds studied. In contrast to conventional cylindrical, unstirred tube models for the determination of wall permeability coefficients, the absorptive clearance calculation can be made based on a physiologically more realistic model-independent, "flat" or "distended," stirred (not well-stirred) intestinal model. Two model-independent terms, "effective intestinal permeability coefficient" and "effective absorptive permeability coefficient," are recommended as the second alternatives. These terms are theoretically valid for compounds that are not metabolized in the intestinal tissue; they represent the overall permeability across the intestinal tissue (from lumen to blood) under given experimental conditions. Potential shortcomings of using dimensionless wall permeability in the conventional absorption modeling are also discussed.

Animals↗

Ion microscopic imaging of calcium during 1,25-dihydroxyvitamin D-mediated intestinal absorption.

A combination of ion microscopic and conventional radionuclide techniques was employed to investigate the temporal-spatial dynamics of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-stimulated intestinal calcium (Ca) absorption. At varying times following the administration of a single intravenous dose of 1,25(OH)2D3 to vitamin D-deficient chicks, transepithelial transport and tissue retention of Ca were quantitated in vivo, using the ligated duodenal loop technique and 47Ca as the tracer. The localization of Ca in the intestinal tissue during absorption was monitored by ion microscopy, using the stable Ca isotope, 44Ca, as the absorbed species. There was little transepithelial absorption of Ca in the vitamin D-deficient animals despite a substantial tissue accumulation of luminally derived Ca, the latter localizing predominantly in the brush border region of the enterocyte, as shown by the 44Ca-ion microscopic images. The early (30 min-1 h) response to 1,25(OH)2D3 was an increased tissue uptake of luminal 47Ca, which also primarily associated with the brush border region, again as shown by ion microscopy. At 2-4 h after the 1,25(OH)2D3 dose, there was a progressive redistribution of Ca from the brush border region throughout the cytoplasm and into the lamina propria. At 8-16 h, 47Ca absorption was maximal and 44Ca was sparsely distributed in the intestinal tissue. 47Ca absorption gradually declined and reached pre-dose levels by 72 h. At this time, tissue 44Ca was again largely limited to the brush border region. These results provide support for the multiple actions of 1,25(OH)2D3 on the intestinal Ca absorption process. The ion microscopic images provided unique information on the specific time-dependent changes in the tissue localization of Ca during the process of its intestinal absorption as affected by 1,25(OH)2D3.

Animals↗

Lipid absorption in the young of protein-deficient rats.

The effect of reduced protein in the diet during pregnancy on the subsequent absorption of triolein and of oleic acid which were infused into the intestine of the young was studied. Pregnant rats were fed diets containing either 24% or 4% casein as the sole source of protein. Control and prenatally protein-deprived (PPD) young were studied at birth before and after suckling, and at 4, 8, and 12 days. Both body weight and the weight and length of intestine were reduced in PPD young. Uptake of triolein from the lumen and retention in enterocytes increased on suckling in newborn control pups, but the amount transferred from or metabolized by the cells did not change. In suckled PPD young, transfer of triolein increased through the enterocyte as well. Unsuckled PPD pups had reduced absorption and retention per enterocyte, per g body weight, per cm gut, and in total. In intestines of control and PPD suckled newborn and postnatal pups, absorption per cell did not differ. Blood lipid levels were increased markedly between 0 and 14 days and tended to decrease to newborn levels by 12 days in both diet groups. Oleic acid absorption in newborn and 12-day PPD pups were reduced in total, per g body weight and per cm of gut. The individual enterocytes were shown to be equally capable of absorption and transfer of triolein and oleic acid. Differences in absorption are related primarily to the numbers of absorptive cells.

Aging↗

Sodium EDTA enhances intestinal absorption of two bisphosphonates.

Bisphosphonates are poorly absorbed when given orally and their absorption is subject to a large inter- and intraindividual variability. This poor absorbability is thought to result, at least in part, from formation of unabsorbable complexes with calcium. It was therefore investigated whether the calcium chelator EDTA could improve intestinal absorption of two bisphosphonates, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), and dichloromethylenebisphosphonate (Cl2MBP). Absorption was assessed indirectly by measuring the suppression of hypercalcemia induced in thyroparathyroidectomized rats by a retinoid. The absorption of AHBuBP was in the range of 1-3%. EDTA increased absorption about tenfold at a AHBuBP dose of 0.6 mg P/kg and about twofold at lower doses, with the minimal effective dose of EDTA being 10 mg/kg. The absorption of Cl2MBP was also increased by EDTA, although to a smaller extent, the lowest effective dose being 100 mg/kg EDTA. Thus, EDTA can, in certain circumstances, increase the intestinal absorption of bisphosphonates. The mechanism might involve an increase in available bisphosphonate and a change in mucosal permeability. The amount of EDTA required is, however, too high for use clinically.

Administration, Oral↗

The assessment of intestinal calcium absorption using stable strontium.

The availability of currently used methods of measuring intestinal calcium absorption is limited by their expense and complexity. Since this measurement may be important in selecting appropriate therapies for patients with osteoporosis, a simpler procedure is required. This paper describes a test which measures the intestinal absorption of stable strontium. A comparison of this test with the single-isotope radio-calcium absorption test in the same group of patients showed a close correlation between the fractional absorption rates of the two elements (r = 0.93, P less than 0.001). Subjects were correctly categorized as having normal or low absorption in 12 out of 13 cases (92%) and the value in the misclassified subject was at the borderline between normal and low calcium absorption. The convenience, low cost, and freedom from radioactivity of stable strontium make it suitable for routine clinical use and, if necessary, repeated testing. If these early results are confirmed, this test will make the assessment of calcium absorption much more widely available.

Aged↗

Effects of calcium and sugars on intestinal manganese absorption.

An in vivo luminal perfusion technique was used to investigate the influence of Ca, Mg, lactose, and glucose on Mn absorption in different segments of the rat intestine. Mn absorption was determined by measuring disappearance of 54Mn activity from the perfusion solution containing 0.1 or 0.01 mmol/L Mn. Na and water absorption were also determined. Mn absorption decreased during the first 30 min of perfusion to reach a steady state thereafter. Ca (1 mmol/L) inhibited Mn absorption in the proximal jejunum and in the colon, whereas Mn absorption was increased by Ca in the distal jejunum. Mg (1 mmol/L), lactose, and glucose (25 mmol/L each) had no effect on Mn absorption in the jejunum. These results can be explained by a direct interaction of Mn and Ca during transcellular Ca transport in the proximal jejunum and colon. The reason for the stimulatory effect of Ca in the distal jejunum is unknown.

Animals↗