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PubMed1989

A comparison of the digestion and absorption of cocoa butter and palm kernel oil and their effects on cholesterol absorption in rats.

Digestion and absorption of cocoa butter and palm kernel oil and their effect on cholesterol absorption were studied in adult male rats. Duodenal and thoracic duct catheters were inserted surgically into the anesthetized rats. After an overnight fast, animals were given a single duodenal dose of an aqueous emulsion containing [1,2-3H]cholesterol and one of the following: corn oil, cocoa butter or palm kernel oil. Digestion and absorption were estimated by recovering the total fatty acids in the thoracic duct lymph over a 24-h collection period (after subtraction of the baseline "endogenous fatty acids" in the lymph). Intestinal absorption of cholesterol into the thoracic duct lymph was reduced significantly (P less than 0.05) in the presence of cocoa butter, compared to absorption when palm kernel oil or corn oil was administered. Compared to the absorption of corn oil (arbitrarily defined as 100%), the absorption of palm kernel oil and cocoa butter was 82 and 63%, respectively. The present study suggests that palm kernel oil absorption was not significantly different from that of corn oil. The lower absorbability of cocoa butter and its inhibitory effect on cholesterol absorption may explain in part why cocoa butter is less hypercholesterolemic and atherogenic than other equally saturated fats.

Analysis of Variance↗
PubMed1978

Vitamin D-3 intestinal absorption in vivo: influence of fatty acids, bile salts, and perfusate pH on absorption.

Intestinal absorption of vitamin D-3 in physiological concentrations was studied in the live unanesthetised rat. In both the jejunum and the ileum a linear relationship was found between the absorption rate of the vitamin and its intraluminal concentration. Increasing the sodium taurocholate concentation in the perfusate above 5mM did not change ileal absorption rate but did decrease jejunal absorption rate. The vitamin's rate of absorption was raised by increases in either the hydrogen ion concentration in vivo is mediated by passive diffusion. The rate of absorption of ttion or the perfusate's flow rate. Addition of 2.5 mM fatty acids of varying chain length and degrees of saturation resulted in a decrease in the rate of vitamin D-3 absorption. These experiments indicate that vitamin D-3 absorption in vivo is mediated by passive diffusion. The rate of absorption of the vitamin is influenced by the composition of the perfusate and the thickness of the unstirred layer.

Animals↗
PubMed1991

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

OBJECTIVE: To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. RESEARCH DESIGN AND METHODS: Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. RESULTS: The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and 68.9 +/- 3.5 from 2.5 h onward; and hexameric insulin 20.7 +/- 1.9 from 0 to 2 h, 45.6 +/- 5.0 from 2.5 to 5 h, and 70.6 +/- 6.3 from 5 h onward. CONCLUSIONS: Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.

Absorption↗
PubMed1975

[Experimental studies on absorption, distribution and excretion of fosfomycin. I. Absorption distribution and excretion of fosfomycin calcium salt (author's transl)].

In order to develop some oral drug preparations containing calcium salt of fosfomycin ((minus)-cis-1,2-epoxypropylphosphonic acid) which is a new antibiotic, the absorption, distribution and excretion were studied when it was administered orally to fasted test animals such as rats, rabbits and dogs. The results are as follows: 1) In the case of rats, the more dose size was increased, the more ratio of excretion in urine as index of gastrointestinal absorption was reduced and ratio of excretion in stools was adversely increased, which suggested a decrease in absorption efficiency. But, as absolute amount of excretion in urine became larger with dose size, it was considered that increase in dose size would serve for elevation of serum levels. 2) When the calcium salt was given to rats and rabbits in form of solution and suspension, the former was more eminent than the latter regarding to absorption efficiency, as generally known. The solution, however, needed relatively large quantity of water to solubilize the calcium salt, and it was not considered that the absorption efficiency depends on only dissolution step or dissolution rate. 3) Difference of the particle size varying from 1.50 mu(bulk particle size) and 0.64 mu(mechanical limit size) measured by Kozeny-Carman method did not affect on the absorption in rats and dogs. So it was considered that the bulk could be use directly without micronizing in manufacturing process for the oral preparations. 4) There were some differences of absorption among the animal species. Good absorption was shown in turn in rats, dogs and rabbits. These differences might depend not only on physiological factors but also anatomical differences such as length of gastrointestinal tract. 5) In rabbits high concentration was observed successively in kidney, lung, heart and so on. In any organ its level decreased similarly to the serum level, not sustaining its initial high concentration. The calcium salt did not possess any affinity to certain organs. 6) In conclusion, though some differences of gastrointestinal absorption were observed among the animal species, fosfomycin calcium salt was well absorbed without problem of micronizing the bulk particles. Moreover, it was perceived that fosfomycin calcium salt, once distributed, would not remain in particular organs, being excreted out of body.

Administration, Oral↗
PubMed1977

GI drug absorption in rats exposed to cobalt-60 gamma-radiation I: Extent of absorption.

The extent of absorption of sulfanilamide, bretylium tosylate, sulfisoxazole acetyl, and riboflavin was determined in rats exposed to 850 rad of cobalt-60 gamma-radiation of sham irradiated. The drug were administered orally at 1 or 5 days postirradiation, and the amount of drug excreted in the urine was used as the measure of absorption. Following intravenous drug administration, there was no difference between irradiated and control animals in the amount of drug excreted in the urine. At 1 day postirradiation, the absorption of sulfanilamide and bretylium was not affected by radiation; the absorption of sulfisoxazole acetyl and riboflavin was increased. The fraction of sulfanilamide excreted in the urine as N4-conjugate was increased at 1 day postirradiation. At 5 days postirradiation, there was no detectable difference between irradiated and control animals in the extent of drug absorption. The effects of radiation on the extent of absorption of orally administered drugs were most pronounced immediately following irradiation. Irradiation apparently does not affect the absorption of drugs that are normally well absorbed or poorly absorbed due to slow transport across the GI mucosa. Following irradiation, there may be an increase in the extent of absorption of drugs that are poorly absorbed due to low aqueous solubility or that are absorbed by a saturable transport mechanism.

Animals↗
PubMed1991

Determination of iron absorption by rat bioassay. Evaluation of methods of dosing 59Fe on radioiron absorption from plant diets.

We studied the potential of an animal model to predict nonheme iron absorption in humans and tested a feasible and easy technique of dosing 59Fe to evaluate bioavailability of dietary nonheme iron. Plant diets containing about 20 ppm or 75 ppm iron were the nonheme iron sources with ferrous sulfate (75 ppm) as a reference. Radioiron was administered by (a) gavaging in water, 1 h after a meal; (b) mixing with the meal; and (c) making a slurry with the meal and gavaging. No significant differences were found (P less than or equal to 0.05) in 59Fe absorption among the three methods of administering radioiron. Absorption of 59Fe was similar to apparent iron absorption for all diets tested, whether the animals consumed the same diet as that of the test meal or a different diet. A high correlation (r = 0.88) obtained between the apparent iron absorption and 59Fe iron absorption for different dosing techniques, indicates that extrinsic iron tag administered by any of these methods is valid to measure nonheme iron absorption. Apparent iron absorption values determined by rats fed 20 ppm or 75 ppm dietary iron from plant sources were similar to reported values for humans. It is concluded that the normal adult rat is an appropriate model to study iron bioavailability of human foods when iron status, maturity, iron intake relative to requirement, and method of measurement are similar to the human situation.

Absorption↗
PubMed1977

Iron absorption from Southeast Asian diets. II. Role of various factors that might explain low absorption.

Previously reported levels of iron absorption from common Southeast Asian meals composed of rice, vegetables, and spices were too low to be consistent with the known prevalence of iron deficiency. In the present paper the cause of the low absorption was systematically sought. Variables investigated comprised methodological errors, factors in the diet such as certain foodstuffs, or contaminants inhibiting the absorption and characteristics of the subjects accompanied by malabsorption of dietary iron. The latter was excluded by comparing the absorption from both wheat rolls and a composit rice meal in Thai and Swedish women using the absorption of a small dose of ferrous ascorbate as a common basis of comparison. Two main factors were identified as causing the low absorption in the previous studies: the homogenization of the labeled meals before serving and the use of rice flour instead of rice. Iron absorption from nonhomogenized meals of identical composition as studied previously was many times higher (on an average 0.16 mg) and was consistent with the actual prevalence of iron deficiency in lower socioeconomic groups of Thais mainly consuming the simple meals studied. Recent modifications of the method to measure nonheme iron absorption from composite meals have thus not only made the determination simpler but also more accurate.

Adult↗
PubMed1974

Food iron absorption in man. Applications of the two-pool extrinsic tag method to measure heme and nonheme iron absorption from the whole diet.

A new radioisotope method to measure iron absorption from the whole diet was used in this study. The method is based on the concept that food iron is absorbed from two pools, the heme iron pool and the nonheme iron pool, which can be especially labeled with two radioiron isotopes given as hemoglobin and as an iron salt. The purpose of this study was to test the accuracy of this two-pool extrinsic tag method. The meals served were composed as an average of 6 wk consumption in the present material of 32 young enlisted men. The mean and total heme and nonheme iron absorption in all the 32 young men was 1.01+/-0.11. This figure agrees well with the mean daily losses expected for this group of subjects (1.0 mg). The conclusion can therefore be made that there are no major systematic errors of the present method to measure the total iron absorption from a mixed diet. In one series a comparison was made of the absorption of heme and nonheme iron from the meals. A significant correlation between the absorption of the two kinds of iron was found. However, a much greater fraction of the heme iron was absorbed (37%) than of the nonheme iron (5%). The absorption both from breakfast and lunch was in two series found to give a good prediction of the total daily nonheme iron absorption. One series was designed to compare the effect of two levels of iron fortification. There was a significant increase in iron absorption when the level of iron fortification of the meals was increased.

Absorption↗
PubMed1985

Immunological control of drug absorption from the gastrointestinal tract: effect of local anaphylaxis on the intestinal absorption of low molecular weight drugs in the rat.

Intestinal absorption of various drugs was examined by means of in situ recirculation technique during local anaphylaxis. The antibody was determined by passive cutaneous anaphylaxis technique in rats immunized once or three times. The optimal condition of local anaphylaxis was determined by the leakage of Evans Blue. The most significant increase in leaks of the dye was observed by the intraluminal challenge with 400 mg of ovalbumin for 10 min in ovalbumin-immunized rats, and this condition was chosen as the optimal condition of local anaphylaxis. Under this condition, intestinal absorption of caffeine, phenylbutazone, and bromthymol blue (BTB) significantly decreased in ovalbumin-immunized rats compared with the control, whereas no significant effect was noted in the intestinal absorption of salicylic acid, quinine, pralidoxime iodide (2-PAM), tetracycline, and phenol red. In normal rats, no significant decrease was obtained in the intestinal absorption of caffeine, phenylbutazone, and BTB. On the other hand, the decreased absorption of BTB was not found in ovalbumin-immunized rats by the intraluminal challenge with bovine gamma-globulin. Furthermore, there was no significant change in the decreased absorption of BTB between rats immunized once and three times. The most effective condition for decreased BTB absorption was observed by the intraluminal challenge with 200 mg of ovalbumin for 10 min in ovalbumin-immunized rats, which almost correlated with the data of Evans Blue leakage. From these observations, it appears that the mucosal immune responses affect the intestinal absorption of low molecular weight drugs.

Anaphylaxis↗