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Results for “INTESTINAL ABSORPTION”

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Limited influence of P-glycoprotein on small-intestinal absorption of cilostazol, a high absorptive permeability drug.

Intestinal transport of the type III phosphodiesterase inhibitor cilostazol was characterized to evaluate the influence of secretory transporter. Intestinal absorption of cilostazol measured by the in situ closed loop method, showed regional differences, with high permeability in the upper part of the small intestine. Intestinal secretory transport of cilostazol at the ileum was tended to be decreased by the increase of tested concentration of cilostazol from 10 to 20 microM when evaluated by means of a Ussing-type chamber method with mounted rat intestinal tissues. Transcellular transport of cilostazol in the basolateral-to-apical direction in LLC-GA5-COL150 cells, which overexpress P-glycoprotein, was higher than that in parental LLC-PK1 cells. In addition, cilostazol reduced the basolateral-to-apical transport and increased the accumulation of [(3)H]daunomycin in LLC-GA5-COL150 cells. Accordingly, cilostazol was demonstrated to be transported by P-glycoprotein, while cilostazol is not likely to cause induction of the expression level of P-glycoprotein by the same manner with rifampin. Apical-to-basolateral transport of cilostazol in Caco-2 cells was increased in a low concentration range, followed by a decrease with further increase of the concentration, while the permeability coefficient of cilostazol was above 1 x 10(-6) cm/s at any concentration. Initial uptake of [(14)C]cilostazol by Caco-2 cells was temperature dependent and was reduced in the presence of unlabeled cilostazol, suggesting that apical uptake is also mediated by a transporter(s). In conclusion, intestinal absorption of cilostazol, which has a high absorptive permeability, may not be significantly hampered by efflux transporters, such as P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Intestinal absorption of fats in children using serum turbidity and triglyceride absorption tests].

Intestinal fat absorption was studied, using serum turbidity and serum triglyceride levels, which were determined before and after a test meal of 2 g neutral fat per kg b.w. in 33 children: 25 controls, four with cystic fibrosis, and four with celiac disease. The results proved that the easy-to-perform serum turbidity test was superior to the triglyceride absorption test in characterizing fat digestion and absorption. The most substantial increase in both tests occurred about three hours after the oral fat load.

Celiac Disease↗

Relationship between glucose transporter and changes in the absorptive system in small intestinal absorptive cells during the weaning process.

In the present study, we investigated the changes in the localization of the glucose transporter GLUT2 and the fructose transporter GLUT5 in small intestinal absorptive cells during postnatal development, especially during the weaning period, using immunohistochemistry and confocal laser scanning microscopy. In the jejunum, GLUT2 was observed within the apical and basolateral membrane domain of absorptive cells, especially in the middle part of the villi. In the suckling rat ileum, GLUT2 was found within the apical and basolateral membrane domain of absorptive cells, but after 18 or 19 days after birth, GLUT2 was found mainly within the apical membrane domain. GLUT5 was observed within the apical membrane domain of absorptive cells in the suckling rat jejunum. In the 18- or 19-day-old rat jejunum, GLUT5 was localized within the apical and basolateral membrane domain of absorptive cells in the lower part of the villi, but after weaning, GLUT5 was found within the apical and basolateral membrane domain of absorptive cells throughout the entire villi. In the suckling rat ileum, there was little GLUT5 in the absorptive cells. In the 18- or 19-day-old rat ileum, GLUT5 was localized within the apical membrane domain of absorptive cells in the lower part of the villi, but after weaning, GLUT5 was observed mainly within the apical membrane domain of absorptive cells throughout the entire villi. These results suggest that the localization of glucose transporters corresponds with a shift from neonatal-suckling to weaned absorptive cells during postnatal development.

Absorption↗

Evaluation of intestinal absorption after longitudinal intestinal lengthening for short bowel syndrome.

PURPOSE: The aim of this study was to answer if the longitudinal intestinal lengthening and tailoring (LILT) by Bianchi, modified by Aigrain, can allow the child to be weaned from parenteral nutrition (PN) and if the length of the bowel after the procedure can influence the results of the absorption test such as Schilling or D-xylose test. PATIENTS AND METHODS: We reviewed the files of 7 children who have had LILT from 1980 to 2003. We performed to explore 2 intestinal function tests: the D-xylose and the Schilling tests. Both were performed early (during the first year after the procedure) and late (during the second year) after the LILT. We used the chi2 and Bartlett's correlation tests for statistical analysis. RESULTS: There were 6 boys and 1 girl. The surgical indication was short bowel syndrome with parenteral nutrition owing to multiple intestinal atresia (2 cases), severe necrotizing enterocolitis with volvulus (1 case), necrotizing enterocolitis (1 case), intestinal atresia with gastroschisis (2 cases), and volvulus owing to malrotation (1 case). The length of the bowel was significantly different before and after LILT (P < .0001). After LILT, the length of the bowel was significantly correlated with the percentage of PN on energy at 6 months (P = .02) and at 12 months (P = .001). Moreover, the length of the bowel after the procedure was significantly correlated with the results of the D-xylose test during the first year (P = .002) but not with the results after the second year. The length after lengthening influenced neither the results of the Schilling test during the first nor those of the second year after. Four patients were weaned from the PN 21 months in average after the LILT (57%); 1 was not because we had only a 2-month follow-up. The average follow-up was 111 (5 months; range, 4-206). CONCLUSION: Longitudinal intestinal lengthening and tailoring for short bowel syndrome is a good option to allow children to be weaned from the PN. The length of the bowel after the procedure can influence the absorption test such as D-xylose during the first postoperative year but not during the second and does not influence the Schilling test. We think it is not necessary to perform these tests during the follow-up of these patients.

Child, Preschool↗

Solubility in and affinity for the bile salt micelle of plant sterols are important determinants of their intestinal absorption in rats.

Intestinal absorption of various plant sterols was investigated in thoracic duct-cannulated normal rats. Lymphatic recovery was the highest in campesterol, intermediate in brassicasterol and sitosterol, and the lowest in stigmasterol and sitostanol. Higher solubility in the bile salt micelle was observed in sitosterol, campesterol, and sitostanol than in brassicasterol and stigmasterol. The solubility of the latter two sterols was extremely low. When the affinity of plant sterols for the bile salt micelle was compared in an in vitro model system, which assessed sterol transfer from the micellar to the oil phase, the transfer rate was the highest in brassicasterol, intermediate in campesterol and stigmasterol, and lowest in sitosterol and sitostanol. Although no significant correlations between lymphatic recovery of plant sterols and their micellar solubility or transfer rate from the bile salt micelle were observed, highly positive correlation was obtained between the lymphatic recovery and the multiplication value of the micellar solubility and the transfer rate. These observations strongly suggest that both solubility in and affinity for the bile salt micelle of plant sterols are important determinants of their intestinal absorption in rats.

Animals↗

Studies on the intestinal absorption of low molecular weight heparin using saturated fatty acids and their derivatives as an absorption enhancer in rats.

Intestinal absorption of low molecular weight heparin (LMWH) as well as unfractionated heparin (UFH) is limited due to its large molecular size and extensive negative charge. Development of its oral formulations would allow outpatient treatment with LMWH and UFH, and contribute a reduction in hospital expenses. The present study was aimed at evaluating the absorption enhancers Labrasol and Gelucire 44/14, which mainly consist of glycerides and fatty acids esters, to improve the intestinal absorption of LMWH. The absorption effects of saturated fatty acids with several carbon chain lengths (C6-C14) were also investigated. LMWH formulated with or without absorption enhancer was administered to the duodenum of fasted rats. The doses of LMWH and absorption enhancer were 20 mg/kg and 30 mg/kg, respectively. Plasma anti-Xa activity was measured as a marker of the LMWH absorption. By administration of the LMWH formulation with Labrasol but not with Gelucire 44/14, the plasma anti-Xa activity was increased to a level above 0.2 IU/ml which is the critical level for elucidation of its anticoagulant activity. Saturated fatty acids also enhanced the intestinal absorption of LMWH, and the order of absorption-enhancing effect was C10=C12>C14>C16>C8> or =C6. These results suggest that the intestinal absorption of LMWH varies with carbon chain lengths of the saturated fatty acids.

Adjuvants, Pharmaceutic↗

Mono-N-carboxymethyl chitosan (MCC), a polyampholytic chitosan derivative, enhances the intestinal absorption of low molecular weight heparin across intestinal epithelia in vitro and in vivo.

The synthesis and evaluation of mono-N-carboxymethyl chitosan (MCC) as an intestinal permeation enhancer for macromolecular therapeutics is presented. MCCs were synthesized from two different viscosity grade chitosans to yield both high and low viscosity grade products. These MCCs were tested on Caco-2 cells for their efficiency to decrease the transepithelial electrical resistance (TEER) and to increase the paracellular permeability of the anionic macromolecular anticoagulant low molecular weight heparin (LMWH). For in vivo studies, LMWH was administered intraduodenally with or without MCC to rats. Both types of experiments were performed at pH 7.4. Results show that both viscosity grade MCCs managed to significantly decrease the TEER of Caco-2 cell monolayers when they were applied apically at concentrations of 3-5% (w/v). Transport studies with Caco-2 cells revealed substantial increases of LMWH permeation in the presence of both viscosity grade MCCs compared with controls. In rats, 3% (w/v) low viscosity MCC significantly increased the intestinal absorption of LMWH, reaching the therapeutic anticoagulant blood levels of LMWH. Both in vitro and in vivo results indicate that the polyampholytic chitosan modification MCC is a suitable and functional polymer for the delivery and intestinal absorption of anionic macromolecular therapeutics like LMWH.

Animals↗

Intestinal absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue. II. In situ and in vitro absorption characteristics of azetirelin from the rat intestine.

Intestinal absorption characteristics of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, were studied in rats by means of in situ closed loop and in vitro everted sac experiments. Plasma concentrations of azetirelin obtained in the in situ closed loop experiments were not significantly different among the intestinal segments. Area under the plasma concentration-time curve (AUC) of azetirelin following administration into the duodenal loop increased in proportion to the dose. The serosal to mucosal concentration ratio of the analogue in the everted sac experiment was constant over the mucosal drug concentration range of 0.01-10 mM. There was no directional difference in the transfer rate of azetirelin across the everted and non-everted sacs of the duodenum. Furthermore, its transport across the duodenum was not influenced by low incubation temperature (25 degrees C), addition of dipeptide (Gly-Gly), or pretreatment of the mucosal surface with 2,4-dinitrophenol, while that of TRH was inhibited under these conditions. These results suggest that the intestinal absorption mechanism of azetirelin is different from that of TRH, and that azetirelin is predominantly transported via a passive diffusion.

Amino Acid Sequence↗