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At least 199 records · Page 11Linked to original sources
PubMed1989

Non-linear intestinal absorption kinetics of cefadroxil in the rat.

Absorption of cefadroxil in a selective intestinal absorption area (the proximal third of the small intestine) of the anaesthetized rat, at seven initial perfusion concentrations, ranging from 0.01 to 10.0 mg mL-1, is shown to be a non-linear transport mechanism. With the aid of computer-fitting procedures based on differential and integrated forms of Michaelis-Menten equation, Vm and Km values of 36.7-37.3 mg h-1 and 12.0-13.0 mg, respectively, were found. The statistical parameters were better than those obtained both for first-order and for combined Michaelis-Menten and first-order kinetics. There is no evidence for substantial passive diffusion processes. The results reported here, together with allometric considerations and literature data analysis, may help to explain some particular non-linear features of plasma level curves associated with the administration of fairly high oral doses of cefadroxil to humans.

Animals↗
PubMed2002

Locally and systemically active glucocorticosteroids modify intestinal absorption of lipids in rats.

Orally administered systemically active steroids enhance the digestive and absorptive functions of the intestine, but their effect on lipid uptake is unknown. The effect of the locally acting steroid budesonide on intestinal absorptive function also is unknown. Accordingly, this study was undertaken to assess the influence of 4 wk of treatment of weaning male rats with a daily oral gavage of budesonide (BUD), prednisone (PRED), or control vehicle on the jejunal and ileal uptake of fatty acids and cholesterol. BUD enhanced jejunal uptake of oleic acid and ileal uptake of linoleic acid. PRED increased jejunal uptake of cholesterol and ileal uptake of lauric, palmitic, linoleic, and linolenic acids. Higher doses of BUD (up to 1 mg/kg) given to adult rats for 2 wk further increased the uptake of some lipids. The changes in the uptake of lipids were not due to variations in the weight of the intestinal mucosa or in the animals' food intake. Ileal ornithine decarboxylase mRNA expression was increased with PRED, but there were no steroid-associated changes in the expression of the mRNA of the early response genes c-myc, c-jun, or c-fos or of proglucagon, the liver fatty acid-binding protein (FABP), the ileal lipid-binding protein, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-6, or IL-10. In summary, treatment of weanling rats with BUD and PRED enhances the uptake of some lipids by a process that is independent of the effects of early response genes and genes encoding cytokines, proglucagon, and FABP.

Adrenal Cortex Hormones↗
PubMed2006

Transporter-mediated intestinal absorption of fexofenadine in rats.

Both influx and efflux transporters are thought to be involved in the intestinal absorption of fexofenadine. The present study examined the influx transporter-mediated intestinal absorption of fexofenadine in rats, focusing on the role of rat oatp3 (Oatp1a5). The intestinal permeability of fexofenadine was evaluated by means of the Ussing chamber method in the presence of a P-glycoprotein inhibitor to block efflux transport. The permeability of fexofenadine from the mucosal to the serosal side was higher than that from the serosal side to the mucosal side. Transport of fexofenadine was saturable, and was significantly decreased by an organic anion transporting polypeptide (oatp) inhibitor. Furthermore, uptake of fexofenadine by Xenopus oocytes expressing rat oatp3 was significantly greater than that by water-injected oocytes, and the affinity of oatp3 for fexofenadine (Km) was about 60 microM, which is comparable with the value obtained by the Ussing chamber method using rat intestinal tissues. These results indicate that oatp3 plays a role as an influx transporter in the intestinal absorption of fexofenadine in rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Intestinal absorption and biliary secretion of cholesterol in rats with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) results in hypercholesterolemia which is attributed to increased production and decreased removal of cholesterol-rich lipoproteins. Adjustments in intestinal absorption are reportedly involved in cholesterol homeostasis. We, therefore, studied the intestinal absorption and biliary excretion of cholesterol in NS. METHODS: We studied intestinal absorption (by in vivo perfusion and in vitro everted sac incubation techniques) and biliary secretion (by common bile duct cannulation) of cholesterol in rats with puromycin-induced NS. The results were compared with those obtained from pair-fed control (PF) animals, those given free access to food (NL) or those fed a hypercholerolemic diet (H-chol group). Micellar solutions of Krebs' phosphate buffer containing trace amounts of [14C]inulin and [3H]cholesterol, as well as different concentrations of unlabeled cholesterol, were used for absorption studies. RESULTS: The NS and H-chol groups showed severe and comparable hypercholesterolemia. No significant difference was found in the rate of biliary cholesterol secretion among the study groups. Likewise, the rates of in vivo and in vitro cholesterol absorptions in the NS and H-chol groups were comparable with one another and similar to those found in the NL and PF groups. The rate of in vitro cholesterol absorption was directly proportional to its concentration in the incubation media at low concentrations. However, the absorption rate showed a pattern consistent with saturable transport at high cholesterol concentrations in all groups. CONCLUSIONS: We conclude that intestinal absorption and biliary secretion of cholesterol are not appreciably influenced by either nephrotic or diet-induced hypercholesterolemia in rats. The data further suggest that cholesterol absorption may be a saturable process.

Animals↗
PubMed1985

Intestinal absorption of arsenate in the chick.

The intestinal absorption of arsenate(As(V)) has been investigated in the chick by means of the in situ ligated duodenal loop technique. By this procedure, it was observed that arsenate is rapidly and essentially completely absorbed (80-95%) from the lumen at As(V) concentrations up to 5 mM, declining to about 50% absorption at 50 mM. Transfer from the intestinal lumen to the mucosal cells at low As(V) concentration (0.1 mM) is rapid, while transfer from the mucosal cells to the body occurs more slowly. At stable As(V) concentrations greater than 1 mM, fractional mucosal cell accumulation of As(V) remains constant, while fractional transfer to the body declines. However, total mucosal accumulation of As(V) and that transferred to the body increase in a linear logarithmic fashion from 0.05 to 5 mm As(V). The results indicate that As(V) readily penetrates both the mucosal and serosal surfaces of the epithelial membrane. Furthermore, arsenate and phosphate do not appear to share a common transport pathway in the duodenum and no evidence was obtained for any interaction between the two at this level. Vitamin D3 administration to rachitic chicks was effective in significantly elevating duodenal arsenate absorption, acting primarily to enhance serosal transport.

Administration, Oral↗
PubMed1986

[Intestinal absorption of calcium gluconate and oseine-mineral complex: an evaluation by conventional analyses].

Calcium (Ca) preparations are widely used in the treatment of osteoporosis, usually as soluble salts. Tolerance might be improved by prescription of slowly dissolved Ca preparations, since Ca is also absorbed distally, even in the colon. In this regard the use of natural forms of Ca might be advantageous, but natural products cannot be labeled reliably for easy evaluation of their absorption. To study the intestinal absorption of an osseino-mineral complex (Ossopan) in comparison with Ca-gluconate, healthy males were investigated by means of conventional blood and urinary measurements before and after ingestion of either substance containing 1.58 g Ca. All subjects were placed on a standard diet 2 days before and during test day. Ca-gluconate (n = 7) evoked a marked and transient rise in plasma ionized calcium; total plasma calcium and urinary calcium followed a parallel course, while plasma and urinary phosphate decreased. After administration of osseino-mineral complex (n = 6), a slow but sustained elevation of plasma ionized calcium was observed while total calcium remained unchanged when corrected by the plasma proteins. Plasma phosphate and proteins increased, as did urinary phosphate. Comparing the 24-hour urine of the test day with that of the previous day, the rise in calcium excretion was slightly greater in the subjects treated by osseino-mineral complex than in those who were given Ca-gluconate, while phosphate excretion increased in the first group and decreased in the second. It is concluded that the bioavailability of Ca in osseino-mineral complex is as good as, if not better than, that of Ca-gluconate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Intestinal absorption of acyclovir beta-glucoside: comparative study with acyclovir, guanosine, and kinetin beta-glucoside.

PURPOSE: To characterize the intestinal absorption of a beta-glucose conjugate of acyclovir (9-[(2-hydroxyethoxy) methyl] guanine, ACV) and compare it to ACV and its analogues in terms of stability and transport by Na+/glucose cotransporter (SGLTI). METHODS: ACVbeta(glc) was enzymatically synthesized using cellulase. Intestinal absorption experiments were performed with rat everted small intestine. Conformation of the glucose moiety was analyzed by NMR spectroscopy. RESULTS: The ACVbeta(glc) was stable on the mucosal side, and was transported to the serosal side in all regions of the small intestine. However, significant contribution of SGLTI to the transport of ACVbetaglc was not observed. NMR spectroscopic analysis indicated that the glucose conformation of ACVbeta(glc) was the 4C1 chair form, identical to beta-glucose or SGLT1-transportable beta-glucosides reported previously. Therefore, other factors such as molecular size and charge due to aglycone may cause no transport of ACVbeta(glc) by SGLT1. On the other hand, the hydrophilicity of ACVbeta(glc) was much higher than of ACV, suggesting water solubility-derived improvement of intestinal absorption of ACV. CONCLUSIONS: ACVbeta(glc) is stable and absorbable, but it is not transported by SGLT1. No involvement of SGLT1 in the ACVbeta(glc) transport is not due to glucose conformation.

Acyclovir↗
PubMed1992

Improvement of intestinal absorption of thyrotropin-releasing hormone by chemical modification with lauric acid.

Intestinal absorption of 125I-labelled lauryl thyrotropin-releasing hormone (Lau-TRH), a novel lipophilic derivative of TRH, was examined by rat in-situ closed intestinal loops. At a dose of 1 mumol per rat into the small intestine, a significant increase in percent of dose in plasma radioactivity of Lau-TRH was observed in comparison with that of TRH. A dose-dependent decrease in percent of dose in plasma radioactivity of TRH was noted, suggesting a saturable process of TRH transport. In contrast, the percent of dose in plasma radioactivity of Lau-TRH increased with increasing dose of Lau-TRH. The stability of TRH and Lau-TRH was studied in plasma and rat small intestinal homogenates. Lau-TRH was more stable than TRH in rat plasma. These results suggest that chemical modification of TRH with lauric acid may not only increase the lipophilicity of TRH but also reduce the degradation of TRH, resulting in the increased plasma radioactivity of TRH. On the other hand, Lau-TRH was gradually converted to TRH in the intestinal mucosal homogenate. These findings indicate that chemical modification of TRH with lauric acid might be a useful approach for improving the intestinal absorption of this peptide.

Animals↗
PubMed1989

Relationship between in vivo first-order intestinal absorption rate constant and the membrane permeability clearance.

An attempt was made to explore the quantitative relationship between the intestinal absorption data obtained from in vivo studies and in situ perfusion studies. The time course of the fraction remaining to be absorbed of L-glucose, erythritol, and urea in the small intestine following the intrajejunal administration to rats was described by a one-compartment model. Thus derived first-order intestinal absorption rate constants (ka) obtained from the in vivo studies in rats were compared with the membrane permeability clearances (CLa,m) estimated in a single-pass perfusion system. Not only were ka and CLa,m in the same increasing order of L-glucose less than erythritol less than urea, but also the operational luminal volumes given as CLa,m/ka were in agreement with the in vivo luminal volume of jejunum estimated by an inulin dilution method. This result suggests that the in vivo intestinal absorption rate (or ka) can be correlated with the intestinal membrane permeability (or CLa,m) by taking the in vivo luminal volume into account.

Animals↗
PubMed1999

Neural modulation of cephalexin intestinal absorption through the di- and tripeptide brush border transporter of rat jejunum in vivo.

Intestinal absorption of beta-lactamine antibiotics (e.g., cefixime and cephalexin) has been shown to proceed through the dipeptide carrier system. In a previous study, nifedipine (NFP), an L-type calcium channel blocker, enhanced the absorption of cefixime in vivo but not in vitro, and it was suggested that neural mechanisms might be involved in the effect of NFP. The aim of the present study was to assess the involvement of the nervous system on the intestinal absorption of cephalexin (CFX). To investigate this, we used a single-pass jejunal perfusion technique in rats. NFP and diltiazem enhanced approximately 2-fold the plasma levels of CFX in treated rats versus untreated controls. NFP also increased approximately 2-fold the CFX level in portal plasma and increased urinary excretion of CFX, thus indicating that CFX did effectively increase CFX intestinal absorption. Perfusing high concentrations of dipeptides in the jejunal lumen competitively reduced CFX absorption and inhibited the enhancement of CFX absorption produced by NFP. Hexamethonium and lidocaine inhibited the effect of NFP, whereas atropine, capsaicin, clonidine, and isoproterenol enhanced CFX absorption by the same order of magnitude as NFP. Thus, complex neural networks can modulate the function of the intestinal di- and tripeptide transporter. Sympathetic noradrenergic fibers, intestinal sensory neurons, and nicotinic synapses are involved in the increase of CFX absorption produced by NFP.

ATP-Binding Cassette Transporters↗
PubMed1985

Impaired intestinal absorption of riboflavin in experimental uremia.

Increased plasma and red blood cell concentrations of riboflavin have been reported in uremia. The possible role of altered intestinal absorption of riboflavin in the genesis of this abnormality is not known. For this reason we examined the intestinal absorption of riboflavin in rats made uremic by subtotal nephrectomy and sham-operated (control) rats in vivo using the recycling perfusion technique and in vitro using the everted-sac technique. Paradoxically, the results showed a significant impairment of intestinal absorption of riboflavin in vivo in uremic rats compared to the control group. However, no significant difference was observed in riboflavin transport in vitro. We conclude that the intestinal absorption of riboflavin is decreased in experimental uremia and cannot account for the reported increase in its plasma and red blood cell concentrations.

Animals↗
PubMed2006

What kinds of substrates show P-glycoprotein-dependent intestinal absorption? Comparison of verapamil with vinblastine.

The influence of P-glycoprotein (P-gp) on intestinal absorption of drugs was investigated by comparison of the uptakes of two P-gp substrates, verapamil and vinblastine, using intestinal segments of wild-type and mdr1a/1b gene-deficient (mdr1a/1b(-/-)) mice, and Caco-2 cells. When [(3)H]vinblastine was injected into intestinal segments of wild-type mice, vinblastine was absorbed from duodenum and ileum, but not from jejunum. This difference among intestinal regions could not be explained by segmental differences of mdr1a mRNA expression. In Caco-2 cells, it was found that vinblastine had a high value of efflux/influx ratio (an index of affinity for P-gp) of 12.1, and a low permeability of less than 1 x 10(-6) cm/sec. The corresponding values for verapamil were 4.9 and 10.6 x 10(-6) cm/sec, respectively. After oral administration of [(3)H]vinblastine to mice, the maximum concentration (C(max)) and the area under the plasma concentration time-curve from time 0 to 24 hr (AUC(0-24 hr)) for mdr1a/1b(-/-) mice were 1.5 times greater than those for wild-type mice, while these parameters were not significantly different between the two strains in the case of [(3)H]verapamil. Therefore, P-gp substrates may be classified into at least two types, i.e., verapamil-type, for which the intestinal absorption is unaffected by P-gp, and vinblastine-type, for which the intestinal absorption is influenced by P-gp. Vinblastine-type P-gp substrates, with low permeability and high affinity for P-gp, would be unfavorable candidates for oral drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism.

Quercetin is a typical flavonoid ubiquitously present in fruits and vegetables, and its antioxidant effect is implied to be helpful for human health. The bioavailability of quercetin glycosides should be clarified, because dietary quercetin is mostly present as its glycoside form. Although quercetin glycosides are subject to deglycosidation by enterobacteria for the absorption at large intestine, small intestine acts as an effective absorption site for glucose-bound glycosides (quercertin glucosides). This is because small intestinal cells possess a glucoside-hydrolyzing activity and their glucose transport system is capable of participating in the glucoside absorption. A study using a cultured cell model for intestinal absorption explains that the hydrolysis of the glucosides accelerates their absorption in the small intestine. Small intestine is also recognized as the site for metabolic conversion of quercetin and other flavonoids as it possesses enzymatic activity of glucuronidation and sulfation. Modulation of the intestinal absorption and metabolism may be beneficial for regulating the biological effects of dietary quercetin.

Animals↗
PubMed1986

Intestinal absorption of aluminum in rats: effect of intraluminal pH and aluminum concentration.

The intestinal absorption of aluminum (Al) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The jejunum-ileum was perfused with media containing 4.63, 9.25 and 18.50 mmol l-1 Al chloride at pH 4.0 and 7.0. Both mucosal retention was not affected by pH but at lower pH more Al was released into the blood. The amount of Al which appeared in the blood was linearly related to the mucosal retention. The Al release into the blood was much less (mumol l-1) than the mucosal retention (mmol l-1). It is concluded that the intestinal absorption of Al is pH- and concentration-dependent.

Aluminum↗
PubMed1984

Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+).

Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique. bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards. Mallards absorbed less dieldrin and mercury than black-crowned night-herons. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

Animals↗
PubMed1990

Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells.

A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of drugs across intestinal epithelium. The cells formed continuous monolayers when grown on permeable filters of polycarbonate. After 10 days in culture, the monolayers had a transmembrane resistance of approximately 260 ohms.cm2 and a cell density of 0.9 x 10(6) cells/cm2. At this time the cells were impermeable to [14C]polyethyleneglycol (MW 4000). These characteristics remained constant for 20 days (i.e., from day 10 to day 30). Six beta-blocking agents with a 2000-fold range of lipophilicity were studied for their transepithelial transport properties. The transport parameters were independent of drug concentration and transport direction. The apparent permeability coefficients ranged from 41.91 +/- 4.31 x 10(-6) cm/s for the most lipophilic drug, propranolol, to 0.203 +/- 0.004 x 10(-6) cm/s for the most hydrophilic drug, atenolol. The transport parameters were compared with those published for rat ileum. The transport rates were similar for four out of five drugs. Atenolol was transported at a slower rate in the Caco-2 model, which may be explained by the fact that the Caco-2 cells form a tighter epithelium than the rat ileal enterocytes. The findings of this paper indicate that Caco-2 cells may be used to model the intestinal absorption of drugs.

Adrenergic beta-Antagonists↗
PubMed1985

Intestinal absorption and excretion of zinc in streptozotocin-diabetic rats as affected by dietary zinc and protein.

65Zn was used to examine the effects of dietary zinc and protein on true zinc absorption and intestinal excretion of endogenous zinc by an isotope dilution technique in streptozotocin-diabetic and control rats. Four groups each of diabetic and control rats were fed diets containing 20 ppm Zn, 20% egg white protein (HMHP); 20 ppm Zn, 10% egg white protein (HMLP); 10 ppm Zn, 20% egg white protein (LMHP); and 10 ppm Zn, 10% egg white protein (LMLP). Measurement of zinc balance was begun 9 d after an i.m. injection of 65Zn. True zinc absorption and the contribution of endogenous zinc to fecal zinc excretion were calculated from the isotopically labeled and unlabeled zinc in the feces, duodenum and kidney. Results from the isotope dilution study indicated that diabetic rats, but not control rats, absorbed more zinc from 20 ppm zinc diets than from 10ppm zinc diets and that all rats absorbed more zinc from 20% protein diets than from 10% protein diets. Furthermore, all rats excreted more endogenous zinc from their intestines when dietary zinc and protein levels resulted in greater zinc absorption. In diabetic and control rats, consuming equivalent amounts of zinc, the amount of zinc absorbed was not significantly different, but the amount of zinc excreted by the intestine was less in the diabetic rats. Decreased intestinal excretion of endogenous zinc may be a homeostatic response to the increased urinary excretion of endogenous zinc in the diabetic rats and may also lead to the elevated zinc concentrations observed in some organs of the diabetic rats.

Analysis of Variance↗