Intestinal permeability and role of P-glycoprotein in intestinal absorption of novel triethylamine containing thiophene S006–830 using single-pass intestinal perfusion in rats

2017 ◽  
Vol 2 (3) ◽  
pp. 163-171 ◽  
Author(s):  
Mahendra Kumar Hidau ◽  
Yeshwant Singh ◽  
Shio Kumar Singh
Keyword(s):  
Intestinal Absorption ◽  
Intestinal Permeability ◽  
Intestinal Perfusion ◽  
Single Pass ◽  
P Glycoprotein

Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat

2017 ◽  
Vol 45 (08) ◽  
pp. 1745-1759 ◽  
Author(s):  
Xin He ◽  
Zi-Jing Song ◽  
Cui-Ping Jiang ◽  
Chun-Feng Zhang
Keyword(s):  
Small Intestine ◽  
Intestinal Absorption ◽  
Rat Model ◽  
Clinical Effectiveness ◽  
Intestinal Perfusion ◽  
Flower Bud ◽  
Transport Pathway ◽  
Absorption Enhancers ◽  
Single Pass

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.

scholarly journals Reply to “Comment on López-Yerena et al. ‘Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats’ Pharmaceutics 2020, 12, 134”

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1221
Author(s):  
Anallely López-Yerena ◽  
Anna Vallverdú-Queralt ◽  
Raf Mols ◽  
Patrick Augustijns ◽  
Rosa M. Lamuela-Raventós ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
Metabolic Profile ◽  
Scientific Community ◽  
Intestinal Perfusion ◽  
Perfusion Technique ◽  
Specific Data ◽  
Single Pass ◽  
Published Paper

Recently, in February 2020, we published a study exploring the intestinal absorption and metabolism of oleocanthal (OLC) in rats. A single-pass intestinal perfusion technique (SPIP) was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Later, comments on our published paper were released, requesting clarification of specific data. In this detailed reply, we hope to have addressed and clarified all the concerns of A. Kaddoumi and K. El Sayed and that the scientific community will benefit from both the study and the comments it has generated.

Quinidine as a Probe for the Role of P-Glycoprotein in the Intestinal Absorption and Clinical Effects of Fentanyl

2004 ◽  
Vol 44 (3) ◽  
pp. 224-233 ◽  
Author(s):  
Evan D. Kharasch ◽  
Christine Hoffer ◽  
T. Gul Altuntas ◽  
Dale Whittington
Keyword(s):  
Intestinal Absorption ◽  
Clinical Effects ◽  
P Glycoprotein

scholarly journals Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 242 ◽  
Author(s):  
David Dahlgren ◽  
Maria-Jose Cano-Cebrián ◽  
Tobias Olander ◽  
Mikael Hedeland ◽  
Markus Sjöblom ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Large Intestine ◽  
Ethylenediaminetetraacetic Acid ◽  
Sodium Dodecyl ◽  
Intestinal Perfusion ◽  
Permeation Enhancers ◽  
Drug Permeability ◽  
Colonic Absorption ◽  
Single Pass ◽  
Perfusion Model

Sufficient colonic absorption is necessary for all systemically acting drugs in dosage forms that release the drug in the large intestine. Preclinically, colonic absorption is often investigated using the rat single-pass intestinal perfusion model. This model can determine intestinal permeability based on luminal drug disappearance, as well as the effect of permeation enhancers on drug permeability. However, it is uncertain how accurate the rat single-pass intestinal perfusion model predicts regional intestinal permeability and absorption in human. There is also a shortage of systematic in vivo investigations of the direct effect of permeation enhancers in the small and large intestine. In this rat single-pass intestinal perfusion study, the jejunal and colonic permeability of two low permeability drugs (atenolol and enalaprilat) and two high-permeability ones (ketoprofen and metoprolol) was determined based on plasma appearance. These values were compared to already available corresponding human data from a study conducted in our lab. The colonic effect of four permeation enhancers—sodium dodecyl sulfate, chitosan, ethylenediaminetetraacetic acid (EDTA), and caprate—on drug permeability and transport of chromium EDTA (an established clinical marker for intestinal barrier integrity) was determined. There was no difference in jejunal and colonic permeability determined from plasma appearance data of any of the four model drugs. This questions the validity of the rat single-pass intestinal perfusion model for predicting human regional intestinal permeability. It was also shown that the effect of permeation enhancers on drug permeability in the colon was similar to previously reported data from the rat jejunum, whereas the transport of chromium EDTA was significantly higher (p < 0.05) in the colon than in jejunum. Therefore, the use of permeation enhancers for increasing colonic drug permeability has greater risks than potential medical rewards, as indicated by the higher permeation of chromium EDTA compared to the drugs.

Sign in / Sign up

Export Citation Format

Share Document