Comparison of intestinal permeability andp-glycoprotein effects on the intestinal absorption of enantiomers of 2-(2-hydroxypropanamido) benzoic acid in rats

Chirality ◽  
2016 ◽  
Vol 29 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Qili Zhang ◽  
Meiyan Zhang ◽  
Danlin Wang ◽  
Yunli Zhao ◽  
Zhiguo Yu
Keyword(s):  
Benzoic Acid ◽  
Intestinal Absorption ◽  
Intestinal Permeability

scholarly journals IMPROVEMENT OF INTESTINAL PERMEABILITY WITH ALANYL-GLUTAMINE IN HIV PATIENTS:

2013 ◽  
Vol 50 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Robério Dias LEITE ◽  
Noélia Leal LIMA ◽  
Christiane Araujo Chaves LEITE ◽  
Calil Kairalla FARHAT ◽  
Richard Littleton GUERRANT ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Intestinal Absorption ◽  
Intestinal Permeability ◽  
High Performance ◽  
Nutritional Supplementation ◽  
Glutamine Supplementation ◽  
Controlled Study ◽  
Before And After ◽  
Double Blinded ◽  
Hiv Aids

ContextGlutamine is the main source of energy of the enterocyte and diarrhea and weight loss are frequent in HIV infected patients.ObjectiveTo determine the effect of alanyl-glutamine supplementation on intestinal permeability and absorption in these patients.MethodsRandomized double-blinded, placebo-controlled study using isonitrogenous doses of alanyl-glutamine (24 g/day) and placebo (glycine, 25 g/day) during 10 days. Before and after this nutritional supplementation lactulose and mannitol urinary excretion were determined by high performance liquid chromatography.ResultsForty six patients with HIV/AIDS, 36 of whom were male, with 37.28 ± 3 (mean ± standard error) years were enrolled. Twenty two and 24 subjects were treated with alanyl-glutamine and with glycine respectively. In nine patients among all in the study protocol that reported diarrhea in the 14 days preceding the beginning of the study, mannitol urinary excretion was significantly lower than patients who did not report this symptom [median (range): 10.51 (3.01–19.75) vs. 15.37 (3.93–46.73); P = 0.0281] and lactulose/mannitol ratio was significantly higher [median (range): 0.04 (0.00–2.89) vs. 0.02 (0.00–0.19); P = 0.0317]. There was also a significant increase in mannitol urinary excretion in the group treated with alanyl-glutamine [median (range): 14.38 (8.25–23.98) before vs 21.24 (6.27–32.99) after treatment; n = 14, P = 0.0382].ConclusionOur results suggest that the integrity and intestinal absorption are more intensely affected in patients with HIV/AIDS who recently have had diarrhea. Additionally, nutritional supplementation with alanyl-glutamine was associated with an improvement in intestinal absorption.

Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting

2009 ◽  
Vol 297 (2) ◽  
pp. G371-G377 ◽  
Author(s):  
Arik Dahan ◽  
Gordon L. Amidon
Keyword(s):  
Intestinal Absorption ◽  
Intestinal Permeability ◽  
Oral Drug ◽  
Dependent Manner ◽  
Therapeutic Action ◽  
Cancer Resistance ◽  
High Permeability ◽  
Small Intestinal ◽  
Intestinal Efflux

Sulfasalazine is characterized by low intestinal absorption, which essentially enables its colonic targeting and therapeutic action. The mechanisms behind this low absorption have not yet been elucidated. The purpose of this study was to investigate the role of efflux transporters in the intestinal absorption of sulfasalazine as a potential mechanism for its low small-intestinal absorption and colonic targeting following oral administration. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on sulfasalazine bidirectional permeability were studied across Caco-2 cell monolayers, including dose-response analysis. Sulfasalazine in vivo permeability was then investigated in the rat jejunum by single-pass perfusion, in the presence vs. absence of inhibitors. Sulfasalazine exhibited 19-fold higher basolateral-to-apical (BL-AP) than apical-to-basolateral (AP-BL) Caco-2 permeability, indicative of net mucosal secretion. MRP2 inhibitors (MK-571 and indomethacin) and BCRP inhibitors [fumitremorgin C (FTC) and pantoprazole] significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport in a concentration-dependent manner. No effect was observed with the P-gp inhibitors verapamil and quinidine. The IC50 values of the specific MRP2 and BCRP inhibitors MK-571 and FTC on sulfasalazine secretion were 21.5 and 2.0 μM, respectively. Simultaneous inhibition of MRP2 and BCRP completely abolished sulfasalazine Caco-2 efflux. Without inhibitors, sulfasalazine displayed low (vs. metoprolol) in vivo intestinal permeability in the rat model. MK-571 or FTC significantly increased sulfasalazine permeability, bringing it to the low-high permeability boundary. With both MK-571 and FTC present, sulfasalazine displayed high permeability. In conclusion, efflux transport mediated by MRP2 and BCRP, but not P-gp, shifts sulfasalazine permeability from high to low, thereby enabling its colonic targeting and therapeutic action. To our knowledge, this is the first demonstration of intestinal efflux acting in favor of oral drug delivery.

Abnormal Intestinal Permeability

1987 ◽  
Vol 150 (6) ◽  
pp. 853-856 ◽  
Author(s):  
N. C. Wood ◽  
I. Hamilton ◽  
A. T. R. Axon ◽  
S. A. Khan ◽  
P. Quirke ◽  
...  
Keyword(s):  
Mental Illness ◽  
Intestinal Absorption ◽  
Intestinal Permeability ◽  
Bowel Disease ◽  
Early Stage ◽  
Aetiological Factor ◽  
Anticholinergic Drugs ◽  
Stage Of Development

Abnormal intestinal absorption has been suggested as an aetiological factor in schizophrenia. A procedure for investigating intestinal permeability was carried out in a group of chronic psychiatric in-patients. A proportion of the subjects studied showed abnormal intestinal permeability which could not be attributed to established bowel disease. Patients who were receiving neuroleptic but not anticholinergic drugs were those most often showing abnormal intestinal permeability. This work is at an early stage of development but preliminary findings suggest that further investigations should be carried out to establish the circumstances in which changes in intestinal permeability may be associated with mental illness.

scholarly journals Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability

2016 ◽  
Vol 19 (3) ◽  
pp. 312 ◽  
Author(s):  
Parvin Zakeri-Milani ◽  
Zohreh Fasihi ◽  
Jafar Akbari ◽  
Ensieh Jannatabadi ◽  
Mohammad Barzegar-Jalali ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Intestinal Absorption ◽  
Intestinal Permeability ◽  
Scanning Calorimetry ◽  
Mole Percent ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
Close Relationship ◽  
Dose Number

Background: We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. Methods: Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. Results: The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. Conclusion: This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Effect of urea on intestinal absorption of salicylic acid, benzoic acid and aminopyrine in rat.

1977 ◽  
Vol 25 (12) ◽  
pp. 3425-3432 ◽  
Author(s):  
YOKO SAKIYA ◽  
MANABU HANANO ◽  
YOSHIKO MIYAUCHI ◽  
HIROKO SAKAI
Keyword(s):  
Salicylic Acid ◽  
Benzoic Acid ◽  
Intestinal Absorption
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