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PubMed1999

A heterogeneous tube model of intestinal drug absorption based on probabilistic concepts.

PURPOSE: To develop an approach based on computer simulations for the study of intestinal drug absorption. METHODS: The drug flow in the gastrointestinal tract was simulated with a biased random walk model in the heterogeneous tube model (Pharm. Res. 16, 87-91, 1999), while probability concepts were used to describe the dissolution and absorption processes. An amount of drug was placed into the input end of the tube and allowed to flow, dissolve and absorb along the tube. Various drugs with a diversity in dissolution and permeability characteristics were considered. The fraction of dose absorbed (Fabs) was monitored as a function of time measured in Monte Carlo steps (MCS). The absorption number An was calculated from the mean intestinal transit time and the absorption rate constant adhering to each of the drugs examined. RESULTS: A correspondence between the probability factor used to simulate drug absorption and the conventional absorption rate constant derived from the analysis of data was established. For freely soluble drugs, the estimates for Fabs derived from simulations using as an intestinal transit time 24500 MCS (equivalent to 4.5 h) were in accord with the corresponding data obtained from literature. For sparingly soluble drugs, a comparison of the normalized concentration profiles in the tube derived from the heterogeneous tube model and the classical macroscopic mass balance approach enabled the estimation of the dissolution probability factor for five drugs examined. The prediction of Fabs can be accomplished using estimates for the absorption and the dissolution probability factors. CONCLUSIONS: A fully computerized approach which describes the flow, dissolution and absorption of drug in the gastrointestinal tract in terms of probability concepts was developed. This approach can be used to predict Fabs for drugs with various solubility and permeability characteristics provided that probability factors for dissolution and absorption are available.

Computer Simulation↗
PubMed1993

Pharmacokinetic analysis of an oral sustained-release diltiazem preparation using multifraction absorption models.

Application of multifraction absorption models to pharmacokinetic analysis of an oral sustained-release diltiazem preparation (HER-SR) was investigated. The plasma diltiazem concentrations after oral administration of the HER-SR preparation were analyzed using both the two-fraction absorption model and the two-step discontinuous absorption model. The two-fraction absorption model was suitable for the pharmacokinetic analysis of the HER-SR preparation, whereas the two-step discontinuous absorption model is often unsuitable for the analysis of sustained-release preparations which disintegrate into fractions with different release characteristics in the gastrointestinal tract. The two-step discontinuous absorption model is usually not applicable to plasma concentration data when the first peak is sharp. MFA-MULTI(V) was shown to be useful for the prediction of the bioavailability in each fraction of HER-SR. It was further demonstrated that a two-fraction absorption model is useful for the comparison of in vitro and in vivo release profiles or evaluating the influence of food on the absorption behavior of HER-SR. In addition, the application of a two-fraction absorption model to population pharmacokinetics of HER-SR was investigated.

Administration, Oral↗
PubMed1975

Lack of relationship of potential difference to fluid absorption in the proximal renal tubule.

Fluid absorption by isolated perfused rabbit proximal convoluted tubules is accompanied by an electrical potential difference (PD), negative in the lumen, when the tubule is bathed by rabbit serum and perfused with an ultrafitrate of that serum. In contrast the PD is positive when the perfusate composition approximates that of fluid in the late proximal tubule in vivo, which lacks glucose, amino acids and bicarbonate. The principal purpose of the present studies was to investigate the characteristics of fluid absorption under these conditions. Proximal convoluted tubules were dissected from rabbit kidneys and perfused in vitro. When the PD was positive, the mean net fluid absorption was 81 nl mm minus 1 min minus 1. The positive PD is caused by a chloride concentration difference across the tubule epithelium (higher in the lumen than in the bath). Elimination of the chloride concentration difference by replacing the bicarbonate in the bath as well as in the perfusate with chloride caused the PD to fall to zero without a significant change in the rate of fluid absorption. Therefore, neither the positive PD nor the chloride concentration difference is significantly related to the fluid absorption. Ouabain inhibited fluid absorption under all of the above conditions, making it likely that the fluid absorption is due to active sodium transport. Although the results are consistent with the generally accepted view that active sodium transport is a major driving force for fluid absorption, the mechanism of anion (chloride) transport is uncertain owing to the lack of correlation between fluid absorption and the transepithelial PD.

Absorption↗
PubMed1980

Effect of flow rate and the extracellular fluid volume on proximal urate and water absorption.

The in vivo microperfusion technique was used to examine the effect of variations in tubular flow rate and the extracellular fluid volume onf [2-14C]-urate and water absorption in the proximal tubule of the rat. In nondiuretic animals, fractional urate absorption was highest at the lowest perfusion rate examined and decreased as the rate of perfusion was increased. Increasing the initial concentration of urate in the perfusion solution had no effect on the fractional absorption of urate. Fractional water absorption was also inversely related to the rate of perfusion. Expansion of the extracellular fluid volume with isotonic saline resulted in rates of urate absorption similar to control values at any given microperfusion rate. Fractional water absorption showed the same flow rate dependency pattern observed in control animals, but at a significantly lower rate of absorption. These studies indicate that fractional urate absorption is dependent upon some parameter of tubular flow rate and that the relationship between urate absorption and perfusion rate is not related to the delivered load of urate per se and is not affected by the state of hydration of the extracellular fluid.

Absorption↗
PubMed2001

Orlistat inhibits dietary cholesterol absorption.

OBJECTIVE: Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration. RESEARCH METHODS AND PROCEDURES: Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous administration of intravenous ([(2)H(6)] cholesterol) and oral ([(2)H(5)] cholesterol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption. RESULTS: In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 +/- 5% and 51 +/- 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 +/- 6% to 44 +/- 5% (p < 0.01). DISCUSSION: These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.

Adult↗
PubMed2004

Relation between calcium absorption and serum calcitriol in normal men: evidence for age-related intestinal resistance to calcitriol.

OBJECTIVE: To obtain information on the causes of age-related bone loss in men and the concomitant decline in calcium absorption. DESIGN: Cross-sectional study. SETTING: Adelaide, South Australia, Australia. SUBJECTS: A total of 95 healthy, Caucasian men (age range 27-87 y). RESULTS: Calcium absorption declined with age (r=-0.46, P<0.0001), as did 24-h urine calcium, phosphate and creatinine (r>-0.21, P<0.05 for all); serum calcitriol and 25 hydroxyvitamin D did not change with age. Calcium absorption was related to serum calcitriol (r=0.20, P=0.05). An inverse relation between the residual deviations in calcium absorption, after allowing for its dependence on calcitriol, and age (F=5.4, P<0.005) was observed. The 24-h urinary calcium, phosphate and creatinine were all related to calcium absorption (r>0.41, P<0.0001). Forearm bone density fell with age (r=-0.45, P<0.0001) but was not related to calcium absorption, or markers of bone turnover. CONCLUSIONS: In healthy Caucasian males (i) calcium absorption falls, but serum calcitriol does not change with age, (ii) the relation between calcium absorption and serum calcitriol changes with age, indicative of an intestinal resistance to calcitriol and (iii) calcium absorption is a significant determinant of 24-h urinary calcium excretion.

Absorptiometry, Photon↗
PubMed2005

Impact of micronutrient dietary intake and status on intestinal zinc absorption in late middle-aged men: the ZENITH study.

BACKGROUND: Adjustments in intestinal absorption and losses of zinc (Zn) are thought to maintain Zn homeostasis when dietary intake levels are altered. Zn status may also influence efficiency of intestinal Zn absorption. OBJECTIVES: To determine the impact of dietary intake and status of some micronutrients on Zn absorption in late middle-aged men. DESIGN AND PARTICIPANTS: Dietary intake and status of Zn, Cu, Fe, vitamin A, C and fibre, and absorption of Zn were measured in 48 men, aged 58-68 y, confined to a metabolic unit and consuming a typical French diet. Dietary intake was estimated using 4-day food-intake records (including the weekend) and the GENI program. To assess Zn status, serum, erythrocyte, urine Zn levels and serum alkaline phosphatase activity were determined. Zn absorption was determined using the isotope double-labelling method. Zn stable isotopic ratios were measured in plasma samples collected before and 48 h after isotope administration using ICP/MS. RESULTS: Zn intake within the group of men varied from 5.7 to 20.5 mg/day and averaged 12.9 mg/day. Serum Zn level varied from 10 to 18 micromol/l and averaged 12.9 micromol/l. Zn absorption varied from 12 to 46% and averaged 29.7%. Zn absorption was not significantly (P > 0.05) correlated with Zn intake or with any of the Zn status parameters. Zn absorption was only slightly negatively correlated with serum and erythrocyte Zn levels and with serum Fe and ferritin levels in this study. CONCLUSION: Zn dietary intake and Zn absorption were satisfactory and led to an adequate Zn status in this population.

Aged↗
PubMed1966

Interference between leucine, isoleucine and valine during intestinal absorption.

1. The reciprocal interference between l-leucine, l-isoleucine and l-valine during absorption was studied in rats both in vivo and with an everted-sac preparation in vitro. 2. After feeding with the amino acids alone there was a considerable increase in their concentration in the intestinal lumen followed by a rapid disappearance, indicating efficient absorption. Absorption was reflected by a high concentration of the respective amino acids in the portal plasma. Isoleucine and valine inhibited the absorption of leucine, and leucine inhibited the absorption of isoleucine and valine. Inhibition of absorption by the interfering amino acid was generally partly overcome after 30-60min., probably through the absorption of the interfering amino acid. At that time the rise in the concentration of the amino acid in portal plasma began. 3. These results were confirmed by experiments in vitro: isoleucine and valine inhibited the absorption rate of leucine, and leucine that of isoleucine and valine. 4. Active absorption of amino acids was rapid at low concentrations and depressed at higher concentrations.

Amino Acids↗
PubMed1977

The effect of calcium on lead absorption in rats.

The effects of Ca2+ on lead absorption as PbCl2 and 203PbCl2 were studied in rats. 1. Doubling of dietary calcium with Ca3(PO4)2 significantly decreased lead absorption as assessed by 203Pb retention, tissue lead concentration, urinary excretion of delta-aminolaevulinate and increased activities of delta-aminolaevulinate dehydratase and ferrochelatase. 2. Similar effects on lead absorption were shown by the Ca2+ salts, Cl-, CO32-, PO43-, SO42-, gluconate and glycerophosphate. 3. CaCl2 and calcium glycerophosphate were found to be most effective in decreasing lead absorption when administered immediately before lead dosage. 4. A negative exponential relationship was found between CaCl2 concentration and 203Pb absorption at 120h. The result suggest that, above 4 mmol of administered calcium, residual lead absorption is unaffected by increasing gastrointestinal calcium concentrations. 5. Increased systemic calcium had no effect on lead retention. 6. Calcium in the concentrations found in domestic hard-water supplies significantly decreased absorption of a solution of 203Pb dissolved in it compared with absorption of 203Pb dissolved in soft or distilled water. 7. Milk and skimmed milk were found to have no effect on 203Pb absorption in rats.

Animals↗
PubMed1998

Intestinal water absorption--implications for the formulation of rehydration solutions.

Absorption of ingested water and most solutes occurs in the proximal small intestine, therefore the rate at which beverages are emptied from the stomach is an important factor in determining the rate of water absorption. In the small intestine, water absorption is brought about by the creation of suitable osmotic gradients that promote net uptake of water from the intestinal lumen. The absorption of solute, especially that brought about by active carriers, are highly effective in creating the osmotic gradients that promote net water uptake. The activation of these transporters also increases the permeability of the mucosa which helps absorption. Moderate hypotonicity of the luminal contents potentiates solute-induced water absorption while hypertonicity slows fluid absorption. Dilute hypotonic glucose-sodium solutions are highly effective oral rehydration solutions, and the type of carbohydrate used does not appear to be important. The addition of other actively absorbed solutes gives little benefit in potentiating water uptake. The inclusion of sodium in rehydration solutions may not be required to stimulate water absorption but probably assists the overall rehydration process. The amount of glucose required to stimulate water absorption is relatively small and for rehydration purposes ingestion of an adequate amount of a dilute solution is more beneficial than drinking a smaller volume of a more concentrated beverage.

Biological Transport↗
PubMed1993

Inhibition of haem-iron absorption in man by calcium.

The inhibiting effect of Ca on non-haem-Fe absorption is well established. Present studies showed that Ca inhibited haem-Fe absorption to the same extent when the same amount of Ca (165 mg Ca as CaCl2) was added to a meal. Attempts were made to examine the mechanism for this inhibition in the present studies. Meat is the only known dietary factor influencing haem-Fe absorption. The present studies were designed to examine whether Ca interfered with the enhancing effect of meat on haem-Fe absorption. We found that the inhibition was the same whether biosynthetically radio-Fe-labelled haemoglobin was given in meals with or without meat. The haem-Fe absorption ratio with:without added Ca was 0.59 (SE 0.07) when Ca was added to a hamburger meal, and 0.52 (SE 0.03) when added to a wheat roll. These values were not significantly different (t 0.95; P = 0.35). The inhibition of haem-Fe absorption by Ca is, thus, a direct effect on the absorption of haem-Fe and not an indirect counteracting effect of the well-known enhancing effect of meat on haem-Fe absorption. Control studies were conducted to ensure that haem-Fe had not been degraded to non-haem-Fe during preparation of the foods. Since Ca inhibits the absorption of haem- and non-haem-Fe to the same extent, the present results strongly suggest that Ca interferes with the transport of Fe through the mucosal cell, and at a late stage, is common for haem- and non-haem-Fe transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Pork meat increases iron absorption from a 5-day fully controlled diet when compared to a vegetarian diet with similar vitamin C and phytic acid content.

Meat increases absorption of non-haem iron in single-meal studies. The aim of the present study was to investigate, over a 5 d period, the potential increasing effect of consumption of pork meat in a whole diet on the fractional absorption of non-haem iron and the total absorption of iron, when compared to a vegetarian diet. A randomised cross-over design with 3 x 5 d whole-diet periods with diets containing Danish-produced meat, Polish-produced meat or a vegetarian diet was conducted. Nineteen healthy female subjects completed the study. All main meals in the meat diets contained 60 g of pork meat and all diets had high phytic acid content (1250 mumol/d). All main meals were extrinsically labelled with the radioactive isotope (59)Fe and absorption of iron was measured in a whole body counter. The non-haem iron absorption from the Danish meat diet was significantly higher compared to the vegetarian diet (P=0.031). The mean fractional absorption of non-haem iron was 7.9 (se1.1), 6.8 (se 1.0) and 5.3 (se 0.6) % for the Danish and Polish meat diets and vegetarian diet, respectively. Total absorption of iron was higher for both meat diets compared to the vegetarian diet (Danish meat diet: P=0.006, Polish meat diet: P=0.003). The absorption ratios of the present study were well in accordance with absorption ratios estimated using algorithms on iron bioavailability. Neither the meat diets nor the vegetarian diets fulfilled the estimated daily requirements of absorbed iron in spite of a meat intake of 180 g/d in the meat diets.

Absorption↗
PubMed2000

Intravesical pressure during irrigating fluid absorption in transurethral resection of the prostate.

OBJECTIVE: In order to control fluid absorption, various approaches are used to reduce intravesical pressure during transurethral resection of the prostate (TURP). With a view to finding a target pressure for such efforts, pressure and fluid absorption were compared in a meta-analysis of four previous studies comprising three different irrigation techniques. MATERIALS AND METHODS: Intravesical pressure was recorded during TURP in which the irrigating fluid was evacuated intermittently (n = 48) by a suprapubic tube (n = 23) or a trocar (n = 30). Fluid absorption was compared with the mean and maximum pressures and the duration of excessive pressure (>2 kPa) over 10-min periods. RESULTS: Mean bladder pressure during fluid absorption was between 1.0 and 2.5 kPa. The maximum pressure during absorption varied greatly during the first 30 min of TURP, but thereafter it ranged between 2 and 3 kPa. Only the duration of pressures >2 kPa increased with fluid absorption (p < 0.02). The maximum pressures were highest with the intermittent technique, while the other indices of intravesical pressure showed the highest values when the suprapubic tube was used. The lowest pressures usually occurred when the trocar was used, but fluid absorption still occurred, as the pressure was much higher during some of these operations. CONCLUSIONS: Fluid absorption occurred at moderate intravesical pressures with all three irrigation techniques. The best strategy for reducing fluid absorption is to keep the pressure below 2 kPa for as long as possible during TURP.

Absorption↗
PubMed2005

Effect of in vivo jet fuel exposure on subsequent in vitro dermal absorption of individual aromatic and aliphatic hydrocarbon fuel constituents.

The percutaneous absorption of topically applied jet fuel hydrocarbons (HC) through skin previously exposed to jet fuel has not been investigated, although this exposure scenario is the occupational norm. Pigs were exposed to JP-8 jet fuel-soaked cotton fabrics for 1 and 4 d with repeated daily exposures. Preexposed and unexposed skin was then dermatomed and placed in flow-through in vitro diffusion cells. Five cells with exposed skin and four cells with unexposed skin were dosed with a mixture of 14 different HC consisting of nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, ethyl benzene, o-xylene, trimethyl benzene (TMB), cyclohexyl benzene (CHB), naphthalene, and dimethyl naphthalene (DMN) in water + ethanol (50:50) as diluent. Another five cells containing only JP-8-exposed skin were dosed solely with diluent in order to determine the skin retention of jet fuel HC. The absorption parameters of flux, diffusivity, and permeability were calculated for the studied HC. The data indicated that there was a two-fold and four-fold increase in absorption of specific aromatic HC like ethyl benzene, o-xylene, and TMB through 1- and 4-dJP-8 preexposed skin, respectively. Similarly, dodecane and tridecane were absorbed more in 4-d than 1-dJP-8 preexposed skin experiments. The absorption of naphthalene and DMN was 1.5 times greater than the controls in both 1- and 4-d preexposures. CHB, naphthalene, and DMN had significant persistent skin retention in 4-d preexposures as compared to 1-d exposures that might leave skin capable of further absorption several days postexposure. The possible mechanism of an increase in HC absorption in fuel preexposed skin may be via lipid extraction from the stratum corneum as indicated by Fourier transform infrared (FTIR) spectroscopy. This study suggests that the preexposure of skin to jet fuel enhances the subsequent in vitro percutaneous absorption of HC, so single-dose absorption data for jet fuel HC from naive skin may not be optimal to predict the toxic potential for repeated exposures. For certain compounds, persistent absorption may occur days after the initial exposure.

Animals↗
PubMed1993

Percutaneous absorption of PCBs from soil: in vivo rhesus monkey, in vitro human skin, and binding to powdered human stratum corneum.

Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental pollutants. The major resident site for these PCBs is the soil, and human skin is frequently in contact with soil. Our objective was to determine the percutaneous absorption of the PCBs Aroclor 1242 and Aroclor 1254 from soil. PCB-contaminated soil was prepared at levels of 44 ppm Aroclor 1242 and 23 ppm Aroclor 1254. PCB concentrations on skin were 1.75 micrograms/cm2 for Aroclor 1242 and 0.91 microgram/cm2 for Aroclor 1254. In vivo percutaneous absorption in the rhesus monkey was determined by urinary and fecal [14C]-PCB excretion for a 5-wk period following topical dosing. Absorption of Aroclor 1242 was determined in vitro with human skin for comparative purposes. In vivo in the rhesus monkey the percutaneous absorption of Aroclor 1242 was 13.8 +/- 2.7 (SD)% of the dose and the absorption of Aroclor 1254 was 14.1 +/- 1.0%. These absorption amounts are similar to the absorption of Aroclor 1242 and 1254 from other vehicles (mineral oil, trichlorobenzene, acetone). With in vitro percutaneous absorption through human skin, most of the Aroclor 1242 and Aroclor 1254 resided in the skin and the amounts were dependent upon dosing vehicle (water > mineral oil > soil). Both PCBs readily partitioned from water into soil and human powdered stratum corneum. By difference the partitioning favored both PCBs going from soil into stratum corneum. These data emphasize the role of soil in percutaneous absorption and provide information for appropriate risk assessment.

Administration, Topical↗
PubMed1994

Delivery of antiglaucoma drugs: ocular vs systemic absorption.

In order to reduce the intraocular pressure antiglaucoma drugs must penetrate into the inner eye. Ocular bioavailability is determined by the ability of drug to penetrate through the cornea and conjunctiva/sclera, and on the other hand, by its elimination from the conjunctival sac. Major part of this elimination is by systemic drug absorption via conjunctiva. Typically conjunctival systemic absorption of drugs is an order of magnitude greater than their ocular absorption. In addition substantial systemic absorption of ophthalmic drugs takes place via nasal mucosa. Systemic absorption of antiglaucoma drugs like beta blocking agents may cause systemic side-effects. The risk of systemic side-effects might be decreased by increasing the ocular/systemic ratio of drug absorption. Several approaches can be used to improve ocular/systemic drug absorption ratio. Firstly, corneal drug permeability is improved. This can be done using different formulations or prodrug derivatives. Secondly, systemic absorption can be decreased e.g. with kinetic drug interactions or drug formulations. Thirdly, the rate of drug delivery can be changed thereby affecting especially the peak concentrations of drug in systemic circulation. Different methods for improvement of ocular delivery relative to the systemic absorption of antiglaucoma drugs are summarized and the impact of systemic pharmacokinetics on the viability of each approach is discussed.

Absorption↗
PubMed1999

Inositol phosphates with different numbers of phosphate groups influence iron absorption in humans.

BACKGROUND: Inositol hexaphosphate (IP(6)) is a well-known inhibitor of iron absorption, whereas the effects of the less-phosphorylated derivatives of IP(6) are less known. OBJECTIVES: The objective was to investigate the effects of inositol tri-, tetra-, and pentaphosphates (IP(3), IP(4), and IP(5), respectively) on iron absorption in humans. DESIGN: Iron absorption was measured in 5 experiments from single meals by extrinsic labeling with (55)Fe and (59)Fe and determination of whole-body retention and the erythrocyte uptake of isotopes. In experiments 1-3 the meals contained white-wheat rolls to which 10 mg P as IP(5), IP(4), or IP(3), respectively, was added. Inositol 1,2,6-triphosphate [Ins(1,2, 6)P(3)] and a mixture of isomers of IP(4) and IP(5) were studied. White-wheat rolls contained 10 mg P as IP(3) + IP(4) and 2 mg P as IP(5) + IP(6) in experiment 4 and 20 mg P as IP(3) + IP(4) and 3 mg P as IP(5) + IP(6) in experiment 5; inositol phosphates were obtained via fermentation of sodium phytate. Each experiment had 8-11 subjects. RESULTS: In experiment 1, iron absorption was reduced by 39%, whereas there was no significant effect on iron absorption in experiments 2 and 3. In experiments 4 and 5, iron absorption was reduced by 54% and 64%, respectively, suggesting that IP(3) and IP(4) contributed to the inhibitory effect. CONCLUSIONS: IP(5) has an inhibitory effect on iron absorption, whereas IP(3) and IP(4) in isolated form have no such effect. IP(3) and IP(4) in processed food contribute to the negative effect on iron absorption, presumably by binding iron between different inositol phosphates. To improve iron absorption from cereals and legumes, degradation of inositol phosphates needs to be to less-phosphorylated inositol phosphates than IP(3).

Absorption↗
PubMed1975

Effect of milk and casein on the absorption of supplemental iron in the mouse and chick.

Milk is an attractive vehicle for introducing iron supplements into iron-deficient infants and children. This study compares the effects of milk and caseins on the whole-body absorption of radioactive iron complexes in an attempt to resolve the controversy over whether milk and its constituent phosphoproteins seriously impair iron absorption. Evidence is presented to clarify the role of the calcium-casein micelles of cow's milk in binding iron donated by the ferric-nitrilotriacetate (NTA) complex. The absorption of iron from isolated Fe(III)-casein complexes was studied in mice as a function of the casein--to--Fe ratio and was compared with the absorption of Fe(III)-NTA at equivalent levels. Even at casein--to--Fe ratios higher than those found in conventional iron-supplemented cow's milk (10-15 mg Fe/qt; casein P:Fe congruent to 34), absorption of iron(III) from the casein or NTA complex was not significantly different. There was no significant difference in the absorption of iron administered to mice and chicks as ferrous ion, ferric-NTA, or ferric fructose; nonfat cow's milk did not inhibit the absorption of these iron compounds. For the chick, in fact, milk significantly enhanced the absorption of iron from the ferric-NTA chelate. In order to affect iron absorption significantly casein would have to be present considerably in excess of that found in conventionally supplemented cow's milk.

Absorption↗