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PubMedDate not supplied

Comparison of effects of natural or artificial rodent diet on etoposide absorption in rats.

The oral administration of etoposide has erratic absorption and low bioavailability. P-glycoprotein (Pgp) located in the intestinal brush-border membrane may pump out orally absorbed etoposide and thus decrease etoposide's absorption. Since flavonoids are abundant in food, we speculated that the common natural rodent diet may contain some flavonoid-related constituents which influence etoposide absorption. We therefore compared the absorption of etoposide's in the everted gut sacs of rats pretreated for 30 minutes with two different diets, natural rodent diet or artificial rodent diet. The effect of quercetin, one of the plant derived flavonoids with Pgp modulating activity, on etoposide's absorption was also compared. The addition of natural rodent diet or quercetin increased etoposide's absorption in everted sacs of jejunum or ileum, in comparison to those added with artificial rodent diet. The enhancing effect of quercetin was compatible with the effect of natural rodent diet in the jejunum and was higher in the ileum. These in vitro data supported the hypothesis that certain dietary components, possibly flavonoid-related compounds, may influence Pgp's function in intestine and thus increase etoposide's absorption. However, when fed with natural rodent diet for one week, a lower enhancing effect on absorption was observed. This may be due to the metabolism of the ingredients with modulating activity to their inactive forms, thus reducing the effect of natural rodent diet on etoposide absorption. The results proved that feeding rats with natural or artificial rodent diet had no obvious effect on etoposide absorption in vivo.

Absorption↗
PubMed1992

Effect of enhanced erythropoiesis on iron absorption.

To examine the influence of erythropoiesis on iron absorption, radioiron absorption tests were performed in normal subjects before and after a course of recombinant erythropoietin. The absorption of heme and nonheme iron from a standard meal was measured in nine subjects, and the absorption of a therapeutic dose of ferrous sulfate given with or without food was determined in an additional 11 subjects. The subcutaneous administration of 100 U recombinant human erythropoietin/kg body weight given on 10 successive days over a 2-week period induced a brisk increase in erythropoiesis and a sharp decrease in iron stores. With the standard meal, there was a modest increase in heme iron absorption from 47.0% to 58.6% (p < 0.05) and a dramatic five-fold rise in nonheme iron absorption from 5.9% to 31.8% (p < 0.001). The absorption of 50 mg iron as ferrous sulfate increased from 2.0% to 17.9% when given with food (p < 0.001) and from 7.0% to 24.6% when given with water (p < 0.001). To assess the effect of erythropoiesis independently of the induced changes in iron status, the absorption data were adjusted to a common serum ferritin level. The relative increase in iron absorption was still significant for both dietary nonheme iron (ratio 2.51, p < 0.02) and ferrous sulfate given with food (ratio 2.99, p < 0.01). It is concluded that the striking enhancement of iron absorption following regular erythropoietin administration in normal subjects is related to the combined effect of diminished iron stores and augmented erythropoiesis.

Adult↗
PubMed1992

Reduction of cholesterol absorption by dietary oleinate and fish oil in African green monkeys.

To determine whether diets enriched in monounsaturated or n-3 fatty acids cause a reduction in cholesterol absorption relative to those more enriched in saturated fatty acids, we measured cholesterol absorption in 18 African green monkeys fed diets enriched in lard, oleinate (oleic acid-rich safflower oil), or fish oil at two levels of dietary cholesterol (0.05 vs. 0.77 mg/kcal). All animals were initially challenged with the lard, high cholesterol diet to ascertain their responsiveness to dietary cholesterol. Based on the results of this challenge, low versus high responders were equally distributed in assignation to the low (n = 6) and high (n = 12) cholesterol regimens. Within each level of dietary cholesterol animals consumed all three dietary fats in random sequences during three experimental phases each lasting 9-12 months with a monkey chow washout period between each phase, so that each animal served as its own control. During each dietary phase measurements of plasma lipids and cholesterol absorption were performed. The animals fed the higher versus lower level of dietary cholesterol had significantly higher plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations and lower percentage cholesterol absorption; high density lipoprotein (HDL) cholesterol levels were not affected by the level of dietary cholesterol. Dietary fish oil resulted in a 20-30% reduction (P less than 0.01) in total plasma and LDL cholesterol and a 30-40% reduction (P less than 0.01) in HDL cholesterol concentrations compared to lard and oleinate regardless of the level of dietary cholesterol. At the high level of cholesterol intake, the oleinate and fish oil diets resulted in significantly lower percentage cholesterol absorption compared to the lard fat diet (35 +/- 2%, 34 +/- 3%, 41 +/- 4%, respectively). At the lower level of dietary cholesterol, percentage cholesterol absorption values were higher than those at the high cholesterol intake (45-52% vs. 34-41%) but were not affected by the type of dietary fat. There was a significant positive correlation between plasma LDL cholesterol concentrations and percentage cholesterol absorption for the oleinate and lard diets at the high level of dietary cholesterol and a significant inverse association between plasma HDL cholesterol and percentage cholesterol absorption. We conclude that the type of dietary fat can influence cholesterol absorption in African green monkeys and that oleinate and fish oil reduce cholesterol absorption relative to lard when a high amount of cholesterol (0.77 mg/kcal) is present in the diet.

Analysis of Variance↗
PubMed2005

[Ultraviolet absorption spectra of iodine, iodide ion and triiodide ion].

Ultraviolet absorption spectra of iodine I2, iodide ion I(-) and triiodide ion I3(-) were studied, and molar absorptivities of these species were determined. Absorption spectrum of I2 aqueous solution appears as an absorption peak at 203 nm with a molar absorptivity of 1.96 x 10(4) L x mol(-1) x cm(-1). Absorption spectrum of I(-) appears as two absorption peaks at 193 and 226 nm with molar absorptivities of 1.42 x 10(4) and 1.34 x 10(4) L x mol(-1) x cm(-1), respectively. When I2 aqueous solution is mixed with KI solution, two absorption peaks appear at 288 and 350 nm, respectively, indicating the formation of I3(-). Using saturation method, molar absorptivities of I3(-) at 288 and 350 nm were determined to be 3.52 x 10(4) and 2.32 x 10(4) L x mol(-1) x cm(-1), respectively.

Absorption↗
PubMed1990

Vitamin D-independent regulation of calcium and phosphate absorption.

Convincing evidence for the stimulatory action of 1,25-dihydroxyvitamin D (1,25(OH2)D) on transcellular absorption of calcium (Ca) and inorganic phosphate (P) has led to the consensus that this hormone is the major regulator of Ca and P absorption. Careful review of the literature, however, suggests important regulation of Ca and P absorption by factors and agents other than those mediated by vitamin D. Thus, in rapidly growing neonatal rats, the intestine is insensitive to vitamin D and Ca absorption is entirely mediated through passive mechanisms. Patterns of change in Ca absorption associated with pregnancy and lactation are identical in vitamin D-replete and vitamin D-deplete rats. The presence of active Ca and P absorption in young, growing rats rigidly deprived of vitamin D and of active Ca and P secretion in mature rats optimally replete with vitamin D, also suggests the participation of non-vitamin D factors in the regulation of intestinal Ca and P absorption. The possibility that Ca and P in the peri-enterocyte environment may regulate their own absorption is discussed. Kinetic analysis of 1,25(OH2)D-induced transport mechanisms indicates that saturation would occur at low substrate concentrations, thus raising the question whether these mechanisms would have major regulatory roles under normal dietary conditions. There is also suggestive evidence indicating that even under conditions of low dietary Ca or P intake, the adaptive changes in intestinal absorption may not be mediated by vitamin D alone. Bile salts, lactose and prolactin are discussed as examples of agents which can stimulate Ca and/or P absorption through vitamin D-independent mechanisms.

Aging↗
PubMed1989

Food iron absorption in idiopathic hemochromatosis.

The relationship between iron status and food iron absorption was evaluated in 75 normal volunteers, 15 patients with idiopathic hemochromatosis, and 22 heterozygotes by using double extrinsic radioiron tags to label independently the nonheme and heme iron components of a hamburger meal. In normal subjects, absorption from each of these pools was inversely correlated with storage iron, as measured by the serum ferritin concentration. In patients with hemochromatosis, absorption of both forms of iron was far greater than would be predicted from the relationship between absorption and serum ferritin observed in normal volunteers. Nevertheless, there was still a modest but statistically significant reduction in absorption of nonheme iron with increasing serum ferritin. This relationship could not be demonstrated in the case of heme iron absorption. In heterozygotes, nonheme iron absorption from a hamburger meal containing no supplementary iron did not differ significantly from that observed in normal volunteers. However, when this meal was both modified to promote bioavailability and supplemented with iron, absorption of nonheme iron was significantly elevated. These studies confirm the presence of excessive nonheme iron absorption even from unfortified meals in patients with idiopathic hemochromatosis and suggest in addition that they are particularly susceptible to iron loading from diets containing a high proportion of heme iron. Impaired regulation of nonheme iron absorption was also observed in heterozygous individuals, but a statistically significant abnormality was demonstrable only when the test meal contained a large highly bioavailable iron supplement.

Adult↗
PubMed1983

Differential absorption of exogenous and endogenous cholesterol in man.

Cholesterol absorption was measured in six patients by a triple-lumen intubation technique: 1) to determine whether isotopic exchange between radiolabeled lumenal cholesterol and unlabeled mucosal cholesterol occurs during cholesterol absorption measurements, and 2) to differentiate the rates of absorption of endogenous cholesterol ([1,2-3H]cholesterol marker given intravenously 6 weeks prior to the tests), exogenous cholesterol ([4-14C]cholesterol marker infused into the proximal duodenum), and total cholesterol mass (sitosterol marker incorporated in the infusion mixture). Measurements of endogenous cholesterol absorption during infusion of a cholesterol-free formula produced identical results whether calculated by the [1,2-3H]cholesterol marker (46.2 +/- 18.2%) or sitosterol marker (44.3 +/- 16.9%) in eight studies. When exogenous cholesterol was administered in liquid formula, its absorption was significantly lower than that of endogenous cholesterol in six out of nine experiments (endogenous = 46.4 +/- 15.4%; exogenous = 33.6 +/- 8.3%; total = 40.9 +/- 10.0%). When exogenous cholesterol was dissolved and administered in triglycerol monooleate, its absorption was higher than that of endogenous cholesterol in four of seven experiments (endogenous = 29.6 +/- 14.5%; exogenous = 33.4 +/- 9.1%; total = 29.9 +/- 12.0%). These comparisons indicate that differential absorption of endogenous and exogenous cholesterol can occur over a 1- or 2-meter segment of the upper small intestine, and that the rate of cholesterol absorption is critically dependent on the physicochemical state of the intralumenal contents. Our results indicate that currently available methods for measurement of cholesterol absorption (most of which are based on the use of radioisotopic sterols for differentiating exogenous from endogenous cholesterol) reliably quantitate the absorption of dietary cholesterol, and that the results of such tests are not significantly confounded by in vivo isotopic exchange.

Aged↗
PubMed1982

Further validation of the plasma isotope ratio method for measurement of cholesterol absorption in man.

Recently we evaluated an isotope ratio method (IRM) for measurement of cholesterol absorption in 14 patients (15 experiments) hospitalized in the metabolic ward by comparing it to simultaneous measurements with a fecal radioactivity method (FRM) and found good to excellent agreement between two procedures (Samuel, P., J. R. Crouse, and E. H. Ahrens, Jr. 1978 J. Lipid Res. 19: 82-93). This comparison has now been extended to additional studies carried out in eight hospitalized patients (19 experiments). Of the 34 comparisons between the IRM and the FRM in our hands, 29 were technically acceptable (chromic oxide fecal recovery >/=80%): percent cholesterol absorption was 43.1 +/- 12% by the FRM and 46.0 +/- 11% by the IRM, exhibiting an accuracy within 3.5% at the 95% and 4.7% at the 99% confidence levels. In addition, various procedural modifications of the IRM were studied in out-patients. The measurement of isotope ratios in a single blood sample (analyzed in sextuplicate) on the third day (or later) following the tests gave identical results to those obtained from six to eight daily blood samplings. Blood samples drawn at any time during the day gave cholesterol absorption values similar to those obtained from samples drawn following an overnight fast. Absorption tests carried out before and 1 hr after breakfast, lunch, or dinner, or giving the oral isotope in three divided daily doses all yielded identical results with tests carried out in the am in the fasting state. Cholesterol absorption was markedly reduced when the oral radiolabeled cholesterol was administered in orange juice vs. liquid formula, milk or a solution of glucose and amino acids, consistent with the well-known fact that gallbladder contraction is a critical requirement of cholesterol absorption. A meal high in cholesterol consumed on the day of the test did not influence the results of the absorption measurements. Furthermore, addition of three eggs per day (~750mg cholesterol) for 3 weeks to a low-cholesterol poly-unsaturated fat diet caused no significant change in percent cholesterol absorption in any of eight patients. We conclude that the isotope ratio method accurately and precisely measures cholesterol absorption in man, and that it is suitable not only for in- but also for out-patient studies.-Samuel, P., D. J. McNamara, E. H. Ahrens, Jr., J. R. Crouse, and T. Parker. Further validation of the plasma isotope ratio method for measurement of cholesterol absorption in man.

Absorption↗
PubMed1995

Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment.

Absorption of dietary cholesterol, campesterol, and sitosterol, cholesterol balance, and fecal excretion of plant sterols were determined in three unrelated patients with phytosterolemia and three healthy volunteers during constant intake of cholesterol and plant sterols using accurate gas-liquid chromatography-mass spectrometry techniques. Each subject received a mixture of [26,26,26,27,27,27-2H6]cholesterol, [6,7,7-2H3]sitostanol, and [6,7,7-2H3]campesterol together with two non-absorbable markers, [5,6,22,23-2H4]sitostanol and chromic oxide. Feces were collected from days 5 to 7 and absorption of different sterols was calculated from the intestinal disappearance of the different sterols relative to [5,6,22,23-2H4]sitostanol and chromic oxide. The results obtained by the two markers were not different and the absorption of cholesterol averaged 53 +/- 4% for the patients (mean +/- SD) and 43 +/- 3% for the volunteers. Campesterol absorption averaged 24 +/- 4% in patients and 16 +/- 3% in healthy volunteers, whereas sitosterol absorption averaged 16 +/- 1% and 5 +/- 1%, respectively. Cholesterol synthesis expressed by body weight varied considerably in the two groups but appeared to be about 5 times lower in patients than in controls. Administration of a high dose of sitostanol (0.5 g t.i.d.) to two patients was followed by a reduction in cholesterol absorption by 24% and 44%, an increase in fecal output of cholesterol and steroids derived from cholesterol and plant steroids, and a marked reduction of serum cholesterol, campesterol, and sitosterol. Under the conditions used, inhibition of cholesterol absorption by sitostanol was not followed by a significant rise in cholesterol synthesis. The time of observation was, however, too short to allow final conclusion on this. The results show that the absolute difference in absorption rate of different sterols between the patients and healthy volunteers was about the same. As a consequence, increasing hydrophobicity causes a relative decrease of absorption rates. Thus, patients with phytosterolemia seem to have a generally increased absorption of sterols rather than a loss of a specific discriminatory mechanism, and oral administration of sitostanol seems to be an interesting new approach for treatment of phytosterolemia.

Absorption↗
PubMedDate not supplied

On the absorption of drugs using chronic dog ileal loop method.

The absorption rate of three model drugs, i.e., pentacaine (highly lipophilic), stobadine (moderately lipophilic) and acetylsalicylic acid (hydrophilic), was studied using the chronic dog ileal loop method. The drugs were dissolved either in 0.9% unbuffered solution of NaCl or in antacid mixture. When using 0.9% NaCl, the half-lives of absorption (t1/2 (dis)) of pentacaine and stobadine were (mean +/- SD) 23.2 +/- 7.8 min and 20.8 +/- 7.2 min, respectively. For stobadine a good agreement was found between its t1/2 (dis) from the ileum and its absorption half-life determined from blood concentrations after oral administration to dogs. The absorption of acetylsalicylic acid accounted for only 10-20% of the dose introduced into the loop over 45 min; thus, a reliable value of t1/2 (dis) could not be determined. The administration of unbuffered solution of NaCl into the loop was accompanied by rapid increase of pH from acidic to basic value. The antacid mixture failed to affect the absorption rate of the drugs studied. Sampling from the ileum was limited to 35-55 min due to rapid absorption of water. These results suggest that: 1) measurement of the absorption rate of some drugs, e.g., stobadine, by using the chronic dog ileal loop method may adequately predict their absorption rate after peroral administration to the dog, 2) interactions of antacids with drug absorption in the ileum may not play a significant role because of the strong buffering capacity of the ileum, and 3) rapid absorption of water from the ileum does not allow to reliably determine the value of t1/2 (dis) for slowly absorbed drugs.

Administration, Oral↗
PubMed1997

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid. 5th communication: factors affecting percutaneous absorption in rats.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. Factors affecting the percutaneous absorption of Am-80 were studied with the intention of obtaining information for toxicity and clinical investigations. The percutaneous absorption of radioactivity was compared after topical application of 0.1% 14C-Am-80 ointment to female rats by simple application (SA), occlusive dressing technique (ODT), and application using lint (AUL). After single topical application to normal skin female rats, the percutaneous absorption of radioactivity was very low with no significant differences in the extent of absorption among the three application methods. In the stripped skin female rats, a distinct increase of the percutaneous absorption was observed indicating that it was markedly affected by the lack of the stratum corneum. Compared with the single dosing, a considerable increase of percutaneous absorption was observed following repetitive topical application once daily for 4 or 7 days to the normal skin female rats. The extent of increase was highest in ODT rats followed by SA rats, but was relatively low in AUL rats. The effects of concentration, dose and application area of 14C-Am-80 ointment on the percutaneous absorption of radioactivity were studied following topical application of 0.002%-0.008% 14C-Am-80 ointment to normal skin male rats by ODT to areas of 72 cm2/kg-360 cm2/kg (5%-25% of the body surface area) at ointment doses of 2g/kg-8 g/kg. When the application area and the amount of ointment applied were fixed at 144 cm2/kg (10% of the body surface area) and 2 g/kg, respectively, the amount of radioactivity absorbed increased in proportion to the 14C-Am-80 concentration in the ointment, whereas the rate of percutaneous absorption, expressed as the percent of dose, was nearly constant. When the 14C-Am-80 concentration in the ointment and the amount of ointment applied were fixed at 0.08% and 2 g/kg, respectively, both the amount of radioactivity absorbed and the rate of percutaneous absorption markedly increased with an increase in the application area. When the concentration of 14C-Am-80 in the ointment was set at 0.008% and the application area at 72 cm2/kg, 144 cm2/kg or 288 cm2/kg (5%, 10% or 20% of the body surface area), the amount of radioactivity absorbed increased as the amount of ointment applied increased for areas of the same, though the rate of percutaneous absorption remained almost constant. When the 14C-Am-80 concentration in the ointment was fixed at 0.008%, the amount of radioactivity absorbed increased markedly about 20-fold with 4-fold simultaneous increases in both the application area (from 72 cm2/kg to 288 cm2/kg) and the amount of ointment applied (from 2 g/kg to 8 g/kg).

Animals↗
PubMed1998

Influence of inert ingredients in pesticide formulations on dermal absorption of carbaryl.

OBJECTIVES: To assess the influence of solvent plus various mixtures on percutaneous absorption and disposition of the carbamate insecticide, carbaryl (CA). ANIMALS: Skin was obtained from the dorsum of 14 female weanling specific-pathogen-free Yorkshire pigs. PROCEDURE: In this 8-hour in vitro flow-through diffusion study, porcine skin sections were dosed with 40 micrograms of CA/cm2 of surface area, different amounts of solvents (40 or 80% acetone or dimethyl sulfoxide [DMSO]), different amounts of a surfactant (0, 1, or 5% sodium lauryl sulfate [SLS]), an insect repellent (0 or 15% diethyl-m-toluamide [DEET]), an insecticide synergist (0 or 2% piperonyl butoxide [PB]), and a CA metabolite (40 micrograms/cm2 1-naphthol [1-NA]). RESULTS: In general, CA absorption was greater from acetone than from DMSO mixtures, and CA penetration into skin and stratum corneum was greater from DMSO at 8 hours. This is consistent with the flux-time profiles, which depicted initial peak flux within 2 to 3 hours for most acetone mixtures, but a slow increase in flux for DMSO mixtures. Irrespective of the solvent, increasing water content in pesticide dosing mixtures significantly increased CA absorption from SLS mixtures only. The SLS also enhanced CA absorption, especially at low solvent concentrations. The DEET significantly reduced CA absorption from acetone, but not from DMSO mixtures, and 1-NA enhanced CA absorption from acetone, but not from DMSO mixtures. Piperonyl butoxide significantly enhanced CA absorption from acetone and DMSO mixtures. However, addition of PB or PB plus SLS did not significantly increase CA flux above that observed from solvent plus surfactant mixtures. CONCLUSIONS: Inert ingredients can modulate percutaneous absorption of toxicologically important pesticides and their effect or activity on CA disposition is dependent on solvent specificity and solvent concentration. Whereas SLS, PB, and 1-NA can enhance pesticide absorption, DEET can reduce absorption.

Acetone↗
PubMed1998

Fluid absorption and the long-term outcome after transcervical resection of the endometrium.

BACKGROUND: Fluid absorption may cause symptoms of acute volume overload and has also been associated with a less favorable outcome after endometrial resection. To further study this topic, we evaluated the incidence of fluid absorption, the factors associated with absorption, and the relationship between fluid absorption and the long-term outcome after TCRE. METHOD: Two hunded and sixty-five women underwent TCRE in which the absorption of irrigating fluid (glycine 1.5%) was measured volumetrically. Physical examinations were made and questions about menstrual blood loss and cyclic pelvic pain were asked before the operation and 12 weeks and 1, 2, and 3 years later. RESULTS: Fluid absorption was increased in patients treated with a GnRH analogue (leuprolide acetate) prior to the TCRE (p<0.007) and also when a submucous myoma was removed during the operation (p<0.0001). About 40% of the women operated on still had menstrual bleeds 1 year later, and this correlated with a larger fluid absorption (p<0.04). Dysmenorrhea disappeared in half the patients, while 17% of those who were pain-free before the TCRE had developed cyclic pelvic pain at 1 year, an outcome also associated with a larger fluid absorption (p<0.02). Pain correlated with lower patient satisfaction, preserved menstrual bleeds, and with the presence of remnants of endometrial tissue as imaged by transvaginal ultrasonography. CONCLUSIONS: Resection of a submucous adenoma increases the risk of fluid absorption during TCRE. The results also indicate that fluid absorption is associated with persistent menstrual bleeding and late development of cyclic pelvic pain.

Absorption↗
PubMed2005

How common is delayed cyclosporine absorption following liver transplantation?

The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA > or =10 mg/kg/day (C(2) monitoring) and in 15 maintenance patients. Patients were categorized as 'normal' absorbers (C(2) exceeding C(4) and C(6)) or 'delayed' absorbers (C(4) or C(6) exceeding C(2)), and as 'good' (>800 ng/mL at C(0), C(2), C(4), or C(6)) or 'poor' absorbers (C(0), C(2), C(4) and C(6) <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had 'normal' CsA absorption and 12 (44%) 'delayed' absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6/15, 40%) or delayed (5/12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C(4). Mean C(0) level was significantly higher in delayed absorbers (282 +/- 96 ng/mL) than in normal absorbers (185 +/- 88 ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C(2) > C(4)) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C(4) in addition to C(2) differentiates effectively between delayed and poor absorbers of CsA such that over- or underimmunosuppression can be avoided.

Adult↗
PubMed2007

Determination of Vitamin D-dependent calcium absorption by 45Ca gavage in the rat.

Precise determination of Vitamin D-dependent intestinal calcium absorption in longitudinal studies is problematic. We have assessed Vitamin D-dependent intestinal calcium absorption by (45)Ca gavage. Rats were gavaged with a 1mL solution containing (45)Ca (CaCl(2), 9.3MBq/mL) maintained at 37 degrees C. Total Ca concentration of the gavage fluid was optimised by comparing the absorption curves for fluids made up to 0.025, 2.025, 4.025 and 40.025 mmol/L with (40)CaCl(2). The effect of varying dietary Ca on fractional Ca absorption was determined in rats fed semi-synthetic diets containing either 0.05%, 0.2%, 0.4% or 1.0% Ca for 50 days. Serum 1,25 dihydroxyvitamin D (1,25D) was determined by radioimmunoassay. Total gavage Ca of 0.025 mmol/L achieved the highest peak fractional absorption and was adopted for all future experiments. Fifty days after allocation to the diets both fractional Ca absorption and 1,25D were highest in rats fed 0.05% Ca and lowest in those fed 1.0% Ca (absorption, P<0.05 and 1,25D, P<0.05). There was a strong logarithmic relationship between 1,25D and fractional Ca absorption (R(2) 0.69, P<0.001). Weekly repetition of the procedure did not cause a fall in haematocrit over 7 weeks. Radiocalcium ((45)Ca) absorption by gavage provides a simple measure of Vitamin D-dependent Ca absorption for repetitive use in longitudinal studies.

Animals↗
PubMed2000

Acute and acclimated digestive responses of the cockle Cerastoderma edule (L.) to changes in food quality and quantity. I. Feeding and absorption of biochemical components.

Cockles Cerastoderma edule were fed two different concentrations ( approximately 0.8 and 2 mm(3) l(-1)) of two diets with different qualities ( approximately 10 and 60% of organic content) which were achieved by mixing different proportions of ashed silt particles with cells of the microalgae Tetraselmis suecica. Clearance, ingestion and absorption rates of organic matter and biochemical components were measured after 3 days (acute response) and 11 days (acclimated response) of exposure to the diets. With low quality diets cockles were found to reject part of the filtered matter ( approximately 25-35%) through pseudofaeces production both in the acute and acclimated responses. In the acute response, absorption rate of organic matter was positively dependent on food quality and quantity, but the physiological response to increasing food concentrations differed with food quality: with low qualities, increasing absorption rate resulted from the simultaneous increase of clearance ( approximately 2 times) and ingestion rate ( approximately 4 times) as well as absorption efficiency of organic matter ( approximately 22%). However, those fed high qualities, were found to compensate increasing food concentration by reducing ( approximately 50%) clearance rate. The resulting moderate increase of ingestion rate ( approximately 1.6 times) was accompanied with a reduction in absorption efficiency ( approximately 20%). Irrespective of food quality and quantity, protein and lipids were absorbed, respectively, with the highest (from 61.7 to 80.0%) and the lowest (from 42.6 to 66.8%) efficiency. Acclimated response was entirely affected by food quality: with low qualities, cockles greatly improved the energetic intake from available ration ( approximately 4 and 2 times, with low and high food concentrations, respectively). Both preingestive and digestive mechanisms were involved in this response: at the preingestive level, clearance rate and preingestive selection efficiency were significantly increased. At the digestive level, cockles were capable of maintaining absorption efficiency of organic matter with rising ingestion rate. On the contrary, acclimation to high quality diets brought about no significant increase in organic absorption rate: with low ration, clearance rate was kept constant, whereas with high ration the increase in clearance and ingestion rate ( approximately 2 times) promoted a compensatory reduction in absorption efficiency. However, the biochemical composition of the absorbed matter was found to be absolutely modified, both at low and high food rations, due to an strong reduction of lipid absorption efficiency. The observed modifications of absorption rate and/or the biochemical composition of the absorbed matter suggests the capability of cockles to adjust the digestive performance.

Journal Article↗
PubMed1988

Sublingual absorption of selected opioid analgesics.

Ongoing interest in the improvement of pain management with opioid analgesics had led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10-minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p less than 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration-time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% +/- 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% +/- 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.

Administration, Sublingual↗
PubMed2005

Ab initio potential energy surfaces, total absorption cross sections, and product quantum state distributions for the low-lying electronic states of N(2)O.

Adiabatic potential energy surfaces for the six lowest singlet electronic states of N(2)O (X (1)A('), 2 (1)A('), 3 (1)A('), 1 (1)A("), 2 (1)A(") and 3 (1)A(")) have been computed using an ab initio multireference configuration interaction (MRCI) method and a large orbital basis set (aug-cc-pVQZ). The potential energy surfaces display several symmetry related and some nonsymmetry related conical intersections. Total photodissociation cross sections and product rotational state distributions have been calculated for the first ultraviolet absorption band of the system using the adiabatic ab initio potential energy and transition dipole moment surfaces corresponding to the lowest three excited electronic states. In the Franck-Condon region the potential energy curves corresponding to these three states lie very close in energy and they all contribute to the absorption cross section in the first ultraviolet band. The total angular momentum is treated correctly in both the initial and final states. The total photodissociation spectra and product rotational distributions are determined for N(2)O initially in its ground vibrational state (0,0,0) and in the vibrationally excited (0,1,0) (bending) state. The resulting total absorption spectra are in good quantitative agreement with the experimental results over the region of the first ultraviolet absorption band, from 150 to 220 nm. All of the lowest three electronically excited states [(1)Sigma(-)(1 (1)A(")), (1)Delta(2 (1)A(')), and (1)Delta(2 (1)A("))] have zero transition dipole moments from the ground state [(1)Sigma(+)(1 (1)A('))] in its equilibrium linear configuration. The absorption becomes possible only through the bending motion of the molecule. The (1)Delta(2 (1)A('))<--X (1)Sigma(+)((1)A(')) absorption dominates the absorption cross section with absorption to the other two electronic states contributing to the shape and diffuse structure of the band. It is suggested that absorption to the bound (1)Delta(2 (1)A(")) state makes an important contribution to the experimentally observed diffuse structure in the first ultraviolet absorption band. The predicted product rotational quantum state distribution at 203 nm agrees well with experimental observations.

Journal Article↗