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PubMed1996

Determination of absorption time of ethanol in social drinkers.

This study was designed to determine the peak, plateau and absorption times of ethanol in a social drinking setting. For the purpose of this study, subjects who had drinking times of 30 min or greater were considered to fit the 'social drinking' category. Healthy subjects (31 male and two female) were tested immediately after they finished drinking. Blood alcohol concentrations (BACs) were measured using a breath testing instrument (Intoxilyzer 5000). Drinking time, type and volume of alcoholic beverage consumed, subject's weight, and a brief description of the breakfast meal were recorded for each subject. The peak, plateau and absorption times were determined for each subject. Peak time was the time interval between the end of drinking and the maximum blood alcohol measurement. Plateau time was the time interval between peak time and the end of absorption time, i.e. the interval between peak time and the beginning of dissipation. Absorption time was defined as the peak time plus plateau time. Among 31 subjects with drinking times of 30 min or greater, 23 (74.2%) had peak and absorption times of < 30 and < 60 min, respectively. Twenty four out of 31 (77.4%) social drinkers had an absorption time of < 60 min, regardless of their peak time. Overall, the average peak and absorption times were 17.4 +/- 17.3 (range 0-74) and 42.2 +/- 31.5 (range 1-130) min. Plateau times averaged 24.9 +/- 23.1 with a range of 0-74 min. It can be concluded from this study that in a social drinking setting, a shorter time to peak and faster rate of absorption may occur when ethanol is consumed over an extended period of time. This is in contrast to results reported in earlier studies involving bolus drinking, where longer absorption times occurred.

Absorption↗
PubMedDate not supplied

Quantitative relationship between rat intestinal absorption and Abraham descriptors.

Literature data on the intestinal absorption of 158 drug and drug-like compounds in rats have been collected, and Abraham descriptors for the set of drugs have been calculated using the method of Platts and Abraham et al. Results show that there is a significant relationship between rat intestinal absorption and the Abraham descriptors. In agreement with the human intestinal absorption model, the dominant descriptors in the rat model are the drug hydrogen bond acidity and basicity. In order to compare the absorption models in humans and rats, the absorption model developed from rats was used to predict the absorption in humans. The rat intestinal absorption model is similar to the human absorption model, and data on rats can effectively be used to predict human intestinal absorption.

Animals↗
PubMed2005

In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies.

The present investigation attempts to increase intestinal permeability and hence absorption of biopharmaceutic classification system (BCS) Class III (cefotaxime sodium (CX)) and Class IV (cyclosporin A (CSA)) drugs by employing certain absorption enhancers. Drugs were co-perfused with sodium caprate (SC, 0.25% w/v), piperine (P, 0.004% w/v) and sodium deoxycholate (SD, 1.0% w/v) separately in rat in situ single pass intestinal perfusion model. These additives increased intestinal permeability (P(app)) and absorption rate constant (K(a)) up to two and fourfold, respectively. SC exhibited substantial absorption enhancement of both CX and CSA, while SD and P enhanced absorption of CX and CSA, respectively. Co-administration of SC significantly enhanced peroral bioavailability of CX (from 29.4 +/- 1.7 to 69.6 +/- 3.2) and CSA (from 18.4 +/- 15.6 to 49.6 +/- 25.1) in rats, while P increased bioavailability of CSA (from 18.4 +/- 15.6 to 33.1 +/- 17.7). Transmission electron microscopy of intestinal mucosa revealed that SC and SD act on lipid and protein domains of absorptive membrane. P showed no effect on intestinal P(app) and oral bioavailability of CX but has a profound effect on CSA, a known P-glycoprotein (P-gp) substrate. These results indicated that P enhances intestinal absorption of CSA by modulating P-gp mediated efflux transport. Release of lactate dehydrogenase in situ from intestinal mucosa in the presence of absorption enhancer was taken as index of its local toxicity. All the absorption enhancers showed significantly less release of LDH compared to positive control, sodium dodecyl sulfate (60% w/v). Overall, the data indicate that the features of these commonly used food ingredients or endogenous bile salts can effectively improve bioavailability of various BCS Class III and Class IV drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.

Paeoniflorin and sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Absorption of Intralipid and interferences from nutrients infused into the peritoneal cavity of the rat.

We studied the peritoneal absorption and elimination of Intralipid after its intraperitoneal and intravenous infusion into rats, by means of a two-compartment model. Follow-up measurements of the plasma triglyceride rate were made. The peritoneal absorption of Intralipid gives the following absorption and elimination constants: Ka (absorption constant from the peritoneal cavity) is 0.106 +/- 0.08 h-1; Ke (elimination constant from the blood stream) is 0.0440 +/- 08 h-1; and BAa (absolute bioavailability) is 84.5 +/- 0.08% 8 hours after infusion. These results show that the intraperitoneal absorption of Intralipid is high and progressive during the first 8 hours, thus supplying the daily caloric needs of the animal through the administration of a single bolus administration, and the plasma triglyceride clearance is faster than the intraperitoneal absorption after the first 6 hours, thus avoiding dangerous overloads. We also studied the behavior of different combinations of glucose, amino acids, and fats infused into the peritoneal cavity of rats in order to observe possible interferences with the absorption of these nutrients. Two microcuries of radioactive L-glucose-1-C14 with 5 mL of 5% D-glucose, with 5 mL of 3.5% amino-acid solution, or with 5 mL of 20% fat emulsion were infused intraperitoneally into three different groups of animals. Slight differences of plasma radioactivity were registered among these three groups 1 hour after infusion. Likewise, small differences of plasma radioactivity were observed between the animals receiving an infusion of 1 microCi of five L-amino-acids-U-C14 diluted with 5 mL of 3.5% amino-acid solution, with 5 mL of 5% glucose solution, or with 5 mL of 20% fat emulsion 4 and 6 hours after infusion. No differences in the plasma triglyceride rates were observed between those groups of animals infused with 5 mL of 20% Intralipid plus 5 mL of glucose solution or with 20% Intralipid plus 3.5% amino-acid solution compared with the group receiving only 5 mL of 20% Intralipid. The infusion of fats does not seem to interfere with that of other substrates, possibly because of the different absorption route (lymphatic for fats and capillary vessels for amino acids and glucose solutions), but further research is needed to reach conclusive results. Perhaps the prolonged administration of fat, together with other substrates, produces precipitates and other galenic problems that hinder absorptive mechanisms of the preparations.

Absorption↗
PubMed2000

Interleukin-11 enhances small intestine absorptive function and mucosal mass after intestinal adaptation.

BACKGROUND/PURPOSE: Interleukin-11 (IL-11) recently has been shown to enhance mucosal mass after massive small bowel resection (MSBR). However, enhanced mucosal mass may not correlate with increased substrate absorption. This study was designed to examine the effect of systemic administration of increasing doses of IL-11 on small intestine absorptive function and mucosal mass after MSBR. METHODS: Twenty-five Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days after resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic pump. The rats were divided into 5 groups based on the content of the pump: group 1 (control, n = 5) received 0.1% bovine serum albumin (BSA) and groups 2 through 5 (n = 5 each) received IL-11 at 250, 500, 750, and 1,000 microg/kg/d, respectively. After a 14-day infusion period, [14C] galactose and [14C] glycine absorption was measured using an in vivo closed-recirculation technique. Mucosal DNA content also was determined for each group. Statistical analysis was performed by analysis of variance and expressed as mean +/-SEM. RESULTS: IL-11 administered at 250 microg/kg/d, a dose used in previous studies, did not significantly affect substrate absorption. However, compared with the control group, administration of higher doses of IL-11 produced a significant increase in substrate absorption and mucosal mass. The dose of IL-11 producing the overall optimal response based on the parameters measured (galactose absorption, 72% increase over control; glycine absorption, 112% increase over control; and DNA content, 98% increase over control) was 750 microg/kg/d. CONCLUSIONS: In addition to an increase in mucosal mass, these data show for the first time that IL-11 enhances absorptive function beyond the normal adaptive response after MSBR. Furthermore, the maximum effect of IL-11 on absorptive function was shown at 750 microg/kg/d, which is 3 times the dose used in previously reported studies. This study suggests that IL-11 may be useful clinically in patients with inadequate intestinal function.

Adaptation, Physiological↗
PubMed1999

Lymphatic absorption of glucose and fatty acids as determined by direct measurement.

BACKGROUND/PURPOSE: Treatment of chylous leaks using enteral feeds supplemented with medium chain triglycerides (MCT) is used widely but often ineffective. Few studies have examined the conventional dogma that MCTs and simple sugars are absorbed directly via the portal system. This study tests the hypothesis that significant absorption of MCTs and simple sugars occurs via the lymphatics. METHODS: A stable, awake rat model with cannulation of the mesenteric lymph duct, portal and jugular veins, and duodenum was used. Venous catheters were infused with saline at 2.5 mL/hr, while the duodenal tube was infused with emulsified fatty acids at 3 mL/hr (0.3% palmitic acid [C16:0] + 0.35% of test nutrient: either Lauric acid [C12:0; n = 5] octanoic acid [C8:0; n = 6] or 3-0-methylglucose, [n = 5].) After 4 hours of stabilization, the animals were given a differentially radiolabeled pulse of palmitic acid plus test nutrient and the subsequent appearance in lymphatic, portal, and jugular systems was measured. Total lymphatic appearance was measured directly; appearance in the portal and jugular systems was measured using the area under the curve method. RESULTS: Results are expressed as mean +/- SD. Palmitic acid: lymphatic absorption (LA), 49.2+/-7.4%; portal venous absorption (PA), 19.8+/-15%; total absorption (TA), 69+/-12.4%. Lauric acid: LA, 32.9+/-6.7%; PA, 7.5+/-2.9%; TA, 40.4+/- 6.3%. Octanoic acid: LA, 5.6+/-2.1%; PA, 27.3+/-6.5%; TA, 32.9+/-4.8%. 3-0 methylglucose: LA, 8.6+/-2.2%; PA 69+/-39%; TA, 76.6+/-39.5. Total lymphatic flow: palmitic plus lauric group, 14+/-2 mL; palmitic plus octanoic, 12.5+/-4.4 mL; palmitic plus 3-0 methylglucose, 12.8+/-2.9 mL. (Total volume measure over 4 hours after giving the radiolabeled pulse.) CONCLUSIONS: The portal venous uptake of the medium chain fatty acid (MCFA), octanoic acid, was not significantly greater than the uptake of the long-chain palmitic acid, but the absorption of lauric acid was less. There are different absorption patterns between different medium-chain fatty acids; however, lymphatic absorption of MCFAs and simple sugars does occur. Total measured absorption of MCFAs is less than that of long-chain fatty acids or sugars. Further work is required to demonstrate the utility of MCT supplementation on nutritional status and lymphatic flow rates in chylous leak syndromes, and to examine the factors that control the results of absorption of fatty acids of varying chain lengths, both in normal and pathological states.

Absorption↗
PubMed1987

Eventual attenuation of hypocalciuric response to hydrochlorothiazide in absorptive hypercalciuria.

The effect of long-term hydrochlorothiazide therapy on renal calcium excretion was measured in 12 well defined cases of absorptive hypercalciuria and 10 of renal hypercalciuria. Patients were studied during a control phase, at 3 to 6 months of therapy and after long-term treatment with hydrochlorothiazide (mean 61 months for absorptive hypercalciuria and 71 months for renal hypercalciuria). Evaluation comprised measurement of urinary calcium and fractional (intestinal) calcium absorption while patients were maintained on a constant metabolic diet (400 mg. calcium per day) for 3 days. In patients with absorptive hypercalciuria urinary calcium decreased significantly at 3 months of treatment (from 266 to 137 mg. per day, p less than 0.001). However, with continued treatment urinary calcium rebounded to 197 mg. per day. Of the patients with absorptive hypercalciuria 50 per cent were hypercalciuric (greater than 200 mg. per day) on long-term treatment, whereas none was hypercalciuric at 3 months. In contrast, urinary calcium in the patients with renal hypercalciuria decreased from 299 to 104 mg. per day (p less than 0.001) at 3 months of treatment and remained reduced (116 mg. per day) during long-term treatment. Intestinal calcium absorption was increased initially and remained unchanged throughout treatment in the patients with absorptive hypercalciuria. In patients with renal hypercalciuria intestinal calcium absorption decreased significantly after short-term treatment with hydrochlorothiazide and remained so after long-term therapy. The results suggest that, unlike patients with renal hypercalciuria, some with absorptive hypercalciuria lose the hypocalciuric effect of hydrochlorothiazide during long-term treatment.

Adult↗
PubMed2003

Effects of maternal ethanol consumption during pregnancy or lactation on intestinal absorption of folic acid in suckling rats.

A fostering/crossfostering analysis of the effects of maternal ethanol exposure on jejunal and ileal folate absorption was performed. Male and female rats were randomized into two groups. In the first group, ethanol-treated rats received ad libitum 5, 10 and 15% ethanol in the drinking fluid during three successive weeks. A consumption of 20% was maintained in this group for 5 additional weeks. Ethanol-treated rats were mated. Group 2 served as the control. To study the effect of chronic alcoholism during lactation or gestation separately, at birth (2nd day postpartum) control newborns were cross-fostered to ethanol dams (EG), and the pups issued from the ethanol treated mothers were cross-fostered to control dams (CG). Thus, three experimental groups of pups were formed: (1) control pups receiving no treatment during gestation and lactation (CG); (2) pups exposed to ethanol only during gestation (GG); and (3) pups exposed to ethanol only during lactation (LG). At 21 days postpartum the jejunal and distal ileum folate absorption was determined in the offspring rats by a perfusion technique. Milk folic acid levels were determined by an immunoluminometric assay. The results showed an increase in jejunal folic acid absorption in offsprings exposed to ethanol only during the lactation period (LG). However, in pups exposed to ethanol only during the gestation period (GG), the jejunal folic acid absorption was significantly increased only at concentrations of 0.25, 0.5 and 2.5 microM. No free folic acid absorption occurred in the distal ileum of control pups (CG) at day 21 at all assayed concentrations but in offsprings exposed to ethanol only during the gestation or lactation periods absorption did take place. Pups exposed to ethanol during the gestation period (GG) showed decreased values in ileum folic acid absorption at the lowest assayed concentration (0.25 microM) compared to values obtained for pups exposed to ethanol only during lactation (LG). Milk folic acid levels were significantly decreased in the ethanol-fed dams on day 21 of lactation. These results indicate that exposure of rats to ethanol during the lactation period affects more severely postnatal development of intestinal functions than ethanol exposure only during gestation. In summary, both the exposure to ethanol itself and the decrease in folic acid intake caused alterations in the function of the intestinal mucosa in the offspring, which in turn altered absorption time and development. However, the present results do not explain how ethanol stimulated intestinal absorption of folic acid in pups exposed to ethanol during the gestation or lactation periods. Further studies are needed.

Administration, Oral↗
PubMed2000

Calcitonin gene-related peptide regulates amino acid absorption across rat jejunum.

The calcitonin gene related peptide (CGRP) is widely distributed in the enteric nervous system and gut afferents. Its role in normal digestion and absorption is not characterised. This study is conducted to elucidate whether CGRP regulates amino acid absorption in the small intestine. In in vivo experiments using the single-pass perfusion technique, intravenous infusion of CGRP (250-750 pmol/kg-min) reduced alanine absorption by 35-40%. The effects were completely blocked by the antagonist hCGRP (8-37). Moreover, intravenous infusion of CGRP antagonist blocked the inhibitory effect of intraluminal capsaicin perfusion on alanine absorption. Similarly, intracerebral injection of CGRP decreased alanine absorption, an effect which was reduced by vagotomy. In vitro experiments using isolated jejunal strips showed that CGRP reduced alanine absorption in a dose-dependent manner. At 6 pM, CGRP decreased alanine absorption by 33%. Similarly, CGRP reduced the absorption of proline and taurine by 20 and 11.5%, respectively. Kinetic studies revealed that CGRP reduces alanine influx into intestinal epithelial cells by inhibiting the affinity of the carriers. It is demonstrated that CGRP is involved in the regulation of jejunal amino acid absorption through intrinsic (enteric) and extrinsic (central) neural mechanisms.

Alanine↗
PubMed2000

Effect of estrogen on intestinal strontium absorption in postmenopausal women.

OBJECTIVES: there is considerable uncertainty about the underlying cause of decreased intestinal calcium absorption that occurs in postmenopausal women. In a previous study, estrogen treatment did not result in an increased intestinal calcium absorption using strontium as a marker. A possible explanation could be that the calcium/strontium load given to the women was too high ( approximately 600 mg Ca), which might result in an insensitive test with respect to the possible stimulation of active strontium transport by estrogen. Therefore, the purpose of this study was to reinvestigate the effect of estrogen on active intestinal strontium absorption using a load of 2.5 mmol of strontium only. METHODS: the effect of estrogen on intestinal strontium absorption was measured in eight normal postmenopausal women. The study included two baseline strontium absorption tests, which were performed with an interval of 10 days for calculating the within subject variation (SER). Thereafter the effect of 2 months of estrogen treatment on intestinal strontium absorption was assessed. Fractional absorption (FC(240)) and the area under the concentration time curve (AUC) 4 h after an oral strontium load of 2.5 mmol were calculated. RESULTS: the within subject SER of FC(240) and AUC(0-240) were 2.3+/-0.76 and 1.2+/-0.41, respectively. FC(240) and AUC(0-240) of strontium were unchanged after treatment with estrogen. CONCLUSIONS: in normal postmenopausal women, we did not find a modulating effect of short-term treatment with a (supra) physiological dose of estrogen on intestinal calcium absorption as measured by the strontium absorption test.

Area Under Curve↗
PubMed2002

Nasal absorption enhancement strategies for therapeutic peptides: an in vitro study using cultured human nasal epithelium.

This study examined the potential usefulness of cultured human nasal epithelium as a model to investigate nasal absorption enhancement strategies for therapeutic peptides. The transport of leucine enkephalin (Leu-Enk) in the presence of bestatin and puromycin, respectively and various combinations of these protease inhibitors with absorption enhancers capable of inhibiting proteases or protecting peptides against protease degradation (glycocholate, dimethyl-beta-cyclodextrin (DM beta CD)) was studied. Epithelial membrane perturbation, protein leakage, bestatin/puromycin absorption and rebound aminopeptidase activity were used as toxicological end-points. The combination of puromycin with glycocholate or DM beta CD resulted in a higher absorption enhancement of Leu-Enk (9-14%) than when the absorption enhancers were combined with bestatin (1-3%) or when the inhibitors were used alone (2-4%). The higher absorption enhancement resulting from the combination of protease inhibitors with absorption enhancers caused a significant reduction of epithelial resistance and increased sodium fluorescein transport. Although only puromycin permeated the human nasal epithelium, both protease inhibitors induced a significant rebound aminopeptidase activity (25-61%), which can be associated with protein leakage (21-46%). This study highlighted (i) the potential usefulness of cultured human nasal epithelium as a model to study nasal absorption enhancement of therapeutic peptides; (ii) further studies using in vivo nasal models are required to ascertain whether the membrane perturbation and cytotoxicity observed with various combinations of the protease inhibitors and absorption enhancers really raise safety concerns.

Absorption↗
PubMed2001

Nasal bioavailability of peptide T in rabbits: absorption enhancement by sodium glycocholate and glycofurol.

The aim of the present study was to investigate the absolute nasal bioavailability of Peptide T from aqueous formulations containing sodium glycocholate, an absorption enhancer with known effect on epithelial tight junctions, and/or glycofurol in a crossover study in rabbits. Additionally, the reversibility of the absorption enhancing effect of sodium glycocholate was studied by applying enhancer and peptide T with different time intervals and calculating Area Under the Curve of the peptide in plasma. It was shown that the bioavailability of Peptide T was significantly enhanced when glycofurol or sodium glycocholate was added to a nasal formulation. The nasal bioavailability of Peptide T in water (control formulation), 5% glycofurol, 5% glycofurol+1% sodium glycocholate and 1% sodium glycocholate was 5.9, 22, 29 and 59%, respectively. As indicated by the differences in t(max), C(max) and time-concentration profiles different patterns of Peptide T absorption were seen from the vehicles containing glycofurol and sodium glycocholate. In the reversibility study, the enhancing effect of sodium glycocholate on nasal absorption of Peptide T was found to be reversible within 4 h. It was concluded, that nasal absorption of Peptide T in rabbits was effectively enhanced by co-administration of sodium glycocholate, which also provided very fast absorption rates as well as a relatively short lasting effect of the absorption enhancing effect. Co-administration of glycofurol leads to enhanced and prolonged absorption of the peptide. Combining the two enhancers did not lead to increased peptide T absorption compared to 5% glycofurol alone.

Absorption↗
PubMed2000

Glucose absorption in acute peritoneal dialysis.

OBJECTIVE: During acute peritoneal dialysis (APD), it is known that glucose found in the dialysate solution contributes to the provision of significant calories. It has been well documented in continuous ambulatory peritoneal dialysis (CAPD) that glucose absorption occurs. In APD, however, it remains unclear how much glucose absorption actually does occur. Therefore, the purpose of this study was to determine whether it is appropriate to use the formula used to calculate glucose absorption in CAPD (Grodstein et al) among patients undergoing APD. METHODS: Actual measurements of glucose absorption (Method I) were calculated in 9 patients undergoing APD treatment for >24 hours who were admitted to the intensive care unit. Glucose absorption using the Grodstein et al formula (Method II) was also determined and compared with the results of actual measurements. The data was then further analyzed based on the factors that influence glucose absorption, specifically dwell time and concentration. RESULTS: The mean total amount of glucose absorbed was 43% +/- 15%. However, when dwell time and concentration were further examined, significant differences were noted. Method I showed a cumulative increase over time. Method II showed that absorption was fixed. This suggests that with the variation in dwell time commonly seen in the acute care setting, the use of Method II may not be accurate. In each of the 2 methods, a significant difference in glucose absorption was noted when comparing the use of 1.5% and 4.25% dialysate concentrations. CONCLUSION: The established formula designed for CAPD should not be used for calculating glucose absorption in patients receiving APD because variation in dwell time and concentration should be taken into account. Because of the time constraints and staffing required to calculate each exchange individually, combined with the results of the study, we recommend the use of the percentage estimate of 40% to 50%.

Absorption↗
PubMedDate not supplied

Intestinal flora and nutrient absorption after intestinal resection.

Intestinal resection results in loss of surface area, motor disruption, and an altered luminal milieu, all of which might influence bacterial growth. Our aim was to determine the effect of extensive intestinal resection in the dog on small intestinal bacterial flora and nutrient absorption. Ten dogs underwent 75% proximal intestinal resection and were killed at either 12 or 40 weeks. Five animals underwent transection alone and were killed at 12 weeks. Ileal aspirates were cultured. Nutritional status and nutrient absorption were measured every 4 weeks. Mean total and anaerobic ileal flora were increased after resection, significantly at 40 weeks. Overall, more cultures from resected animals had more than 5x10(6) total bacteria (6 of 10 vs. 0 of 10, P<0.05) and more than 10(5) anaerobic bacteria (5 of 10 vs. 0 of 10, P<0.05) than unoperated animals. Total but not anaerobic bacteria were increased after transection alone. Ingestion and absorption of carbohydrate decreased but absorption efficiency was maintained. Nitrogen intake decreased but excretion and absorption were unchanged. Fat intake decreased and excretion was unchanged resulting in decreased absorption. Mean intake, excretion, and absorption of nutrients were not influenced by the presence of significant growths of total (>5x10(6)/ml) or anaerobic (>10(5)/ml) bacteria. It was concluded that (1) 75% proximal intestinal resection results in significantly more aerobic and anaerobic bacteria in the ileal remnant; (2) intestinal bacterial content does not correlate with absorption of nutrients; and (3) the colon, and particularly colonic bacteria, may have a more important role in nutrient absorption than luminal flora in the small intestine after resection.

Absorption↗
PubMed1975

Studies on the absorption and retention of calcium and phosphorus by young and mature Ca-deficient sheep.

1. A combination of a mineral balance and a radioactive technique has been used to study the effects of increased levels of dietary calcium and phosphorus on the Ca and P metabolism of young and mature wether sheep previously made Ca-deficient. 2. Ca absorption was directly related to Ca intake until an absorption maximum was reached. Young animals absorbed dietary Ca more efficiently than mature animals and had a much higher maximum rate of absorption. Apparent P absorption was directly related to P intake and maximum P absorption was also higher for the young animals. 3. Excretion of Ca in the urine and into the intestine was not altered by changes in Ca intake. Excretion of P in the urine, however, varied considerably and it is suggested that this process may be largely responsible for P homoeostasis. 4. Ca retention was directly related to Ca absorption. Maximum retention was considerably higher for the young animals than for the mature animals and occurred for each group of animals at exactly the same dietary intake as maximum Ca absorption. 5. Ca and P were retained in a constant ratio of 1-25:1 and the results suggested that P retention was controlled by the rate of Ca retention. 6. Bone turnover was higher for the young than for the mature animals. Animals mobilized skeletal Ca when receiving the Ca-deficient diet and replaced their Ca losses when the dietary Ca was plentiful by changing the relative rates of bone resorption and bone accretion. Although bone resorption was mainly responsible for Ca homoeostasis, bone accretion appeared to play some part in the young animals. 7. Maximum retention of Ca occurred just as the rate of bone resorption became zero and was equal to the rate of bone accretion. The lower maximum retention of Ca for mature animals was due to a lower rate of bone accretion. 8. Results suggested that when bone resorption ceased, Ca absorption was regulated by homoeostatic mechanisms at a level just sufficient to maintain maximum retention, and that the maximum rates of absorption measured may not have been true maximum rates. 9. The consequences of a relationship between bone accretion and maximum Ca retention are discussed with reference to older, pregnant and lactating animals.

Age Factors↗
PubMed1998

Nasal absorption kinetic behavior of azetirelin and its enhancement by acylcarnitines in rats.

PURPOSE: The long-term stability and nasal absorption characteristics of a basic nasal formulation of azetirelin, a thyrotropin-releasing hormone analog and its absorption enhancement by incorporation of acylcarnitines in the formulation were investigated. METHODS: The long-term stability of basic nasal azetirelin formulations at 25 degrees C was predicted by calculation from the Arrhenius plot of the data on 6 months' storage at 40, 50 and 60 degrees C. Nasal azetirelin absorption characteristics were kinetically examined by intranasal administration to rats, determination of plasma azetirelin level by radioimmunoassay, and fitting the data to a two-compartment model including absorption rate. RESULTS: Basic nasal azetirelin formulations of pH 4.0 and pH 5.1 were predicted to be highly stable. Residual azetirelin after 2 years storage at 25 degrees C was greater than 95%. Nasal absorption characteristics of this formulation in the pH 4.0-6.3 range showed pH-dependency, with pH 4.0 showing the highest absolute bioavailability (Bioav) of 17.1%. This nasal Bioav was 21 times greater than that of oral administration (0.8%). Acylcarnitines with 12 or more carbon atoms in the acyl chain greatly enhanced nasal absorption of azetirelin: Bioavs with lauroylcarnitine chloride (LCC) and palmitoylcarnitine chloride were 96.9% and 72.9%, respectively. This enhancement by LCC plateaued at the low concentration of 0.1%. CONCLUSIONS: The basic nasal azetirelin formulation at pH 4.0 is stable and shows adequate absorption, with nasal absorption having greater Bioav than oral absorption. The 12-carbon acylate LCC was the strongest enhancer among acylcarnitines and provided near-total delivery of the administered dose to the blood.

Absorption↗
PubMed1996

Tmax: an unconfounded metric for rate of absorption in single dose bioequivalence studies.

PURPOSE: While peak drug concentration (Cmax) is recognized to be contaminated by the extent of absorption, it has long served as the indicator of change in absorption rate in bioequivalence studies. This concentration measure per se is a measure of extreme drug exposure, not absorption rate. This paper redirects attention to Tmax as the absorption rate variable. METHODS: We show that the time to peak measure (Tmax), if obtained from equally spaced sampling times during the suspected absorption phase, defines a count process which encapsulates the rate of absorption. Furthermore such count data appear to follow the single parameter Poisson distribution which characterizes the rate of many a discrete process, and which therefore supplies the proper theoretical basis to compare two or more formulations for differences in the rate of absorption. This paper urges limiting the use of peak height measures based on Cmax to evaluate only for dose-dumping, a legitimate safety concern with any formulation. These principles and techniques are illustrated by a bioequivalence study in which two test suspensions are compared to a reference formulation. RESULTS: Appropriate statistical evaluation of absorption rate via Tmax supports bioequivalence, whereas the customary analysis with Cmax leads to rejection of bioequivalence. This suggests that the inappropriate use of Cmax as a surrogate metric for absorption rate contributes to the unpredictable and uncertain outcome in bioequivalence evaluation today.

Absorption↗