Intestinal absorption mechanism of amphoteric β-lactam antibiotics I: Comparative absorption and evidence for saturable transport of amino-β-iactam antibiotics by in situ rat small intestine

1981 ◽  
Vol 70 (7) ◽  
pp. 768-772 ◽  
Author(s):  
Emi Nakashima ◽  
Izumi Kagami ◽  
Akira Tsuji ◽  
Tsukinaka Yamana
2001 ◽  
Vol 120 (5) ◽  
pp. A183-A183
Author(s):  
H KOBAYASHI ◽  
H NAGATA ◽  
S MIURA ◽  
T AZUMA ◽  
H SUZUKI ◽  
...  

2017 ◽  
Vol 45 (08) ◽  
pp. 1745-1759 ◽  
Author(s):  
Xin He ◽  
Zi-Jing Song ◽  
Cui-Ping Jiang ◽  
Chun-Feng Zhang

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.


1979 ◽  
Vol 237 (5) ◽  
pp. E399 ◽  
Author(s):  
Y F Shiau ◽  
C Umstetter ◽  
K Kendall ◽  
O Koldovsky

Fatty acid esterification was measured in fetal jejunal and ileal isografts implanted under the kidney capsules of adult host rats and compared to the age-controlled intestine grown in situ. Studies were conducted on the 21st, 35th, 49th, and 63rd postconceptional days, corresponding to prenatal, suckling, weaning, and weaned rats. Substantial fatty acid esterification activity was found in prenatal jejunum but not in ileum. A proximal-distal gradient of fatty acid esterification was observed in all groups grown in situ, but not in isografts. The monoglyceride pathway (MG-P) accounted for about one-third of total fatty acid esterification (TFAE) in jejunum grown in situ and remained constant through the study. In the ileum, MG-P was the major esterification pathway during the first 4 postnatal weeks, but decreased progressively after weaning to become insignificant in adult rats. TFAE fell in the jejunal isografts, whereas it increased in the ileum. MG-P remained as the major pathway in the implanted jejunum and ileum. Our studies suggest that luminal contents are probably the most important modulator for the development and maintenance of intestinal fatty acid esterification, and "fetal programming" manifested by changes in fatty acid esterification mechanisms in the isografts is less important.


1989 ◽  
Vol 257 (4) ◽  
pp. G489-G495 ◽  
Author(s):  
H. Daniel ◽  
C. Fett ◽  
A. Kratz

The intervillous pH profiles along the crypt villus axis in different regions of the rat small intestine were measured in vitro by using pH-sensitive liquid ion-exchanger microelectrodes. A characteristic pH profile was observed in the duodenum and jejunum. A region of low pH was detected in the upper parts of the villi (pH 6.65 +/- 0.06 to 6.85 +/- 0.07), whereas pH at the villus base was always higher. In the ileum no gradient was observed (pH 7.26 +/- 0.05 to 7.31 +/- 0.05). Preincubation of the tissue in situ with 10 mM theophylline for 1 h caused an increase in the villus base pH in the jejunum (pH 7.24 +/- 0.04) and ileum (7.44 +/- 0.04) followed by a subsequent increase of the pH in the upper part of the villi. These results indicate that the low pH in the upper intervillous space may be related to H+ secretion occurring from the mature enterocytes, whereas the crypt cells may secrete a rather neutral or slightly alkaline fluid. Alkaline secretion from the crypts may be increased by theophylline, which changes the levels of cyclic nucleotides in the mucosa.


1978 ◽  
Vol 1 (2) ◽  
pp. 122-131 ◽  
Author(s):  
MASATO YASUHARA ◽  
HIROYUKI KOBAYASHI ◽  
TOSHIKIRO KIMURA ◽  
SHOZO MURANISHI ◽  
HITOSHI SEZAKI

2020 ◽  
Author(s):  
Cheng Wang ◽  
Yimeng Zhou ◽  
Xiaohong Gong ◽  
Li Zheng ◽  
Yunxia Li

Abstract Background: 2,3,5,4'-tetrahydroxystilbence-2-O-β-D-glucoside(TSG) is a polyhydroxyphenolic compound, which exhibited a broad spectrum of pharmacological activities, such asanti-inflammatory, anti-depression, anti-oxidation and anti-atherosclerosis.However, the compound had poor bioavailability and the underlying absorption mechanisms had not been studied. Therefore, the purpose of this study was to investigate the intestinal absorption mechanism of TSG. Methods: This study used Caco-2 cell monolayer model and single-passintestinal perfusion modelto explore the gastrointestinal absorption mechanisms of TSG. The effects of basic parameters such as drug concentration, time and pH on the intestinal absorption of TSG were analyzed by high performance liquid chromatography.The absorption susceptibility of TSG to three inhibitors, P-gp inhibitors verapamil hydrochloride and quinidine, and MRP2 inhibitor probenecid were also assessed. Results: TSG was poorly absorbed in the intestines and the absorption of TSG in stomach is much higher than that in intestine. Both in vitro and in situ experiments showed that the absorption of TSG was saturated with increasing concentration and it was better absorbed in a weakly acidic environment pH 6.4. Moreover, TSG interacts with P-gp and MRP2, and TSG was not only the substrate of the P-gp and MRP2, but also affected the expression of P-gp and MRP2. Conclusions: It wasconcluded that the gastrointestinalabsorption mechanisms ofTSG involved processes passive transport and the participation ofefflux transporters.


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