Prediction of in vivo intestinal absorption enhancement on P-glycoprotein inhibition, from rat in situ permeability

2005 ◽  
Vol 94 (8) ◽  
pp. 1694-1704 ◽  
Author(s):  
Manthena V.S. Varma ◽  
Ramesh Panchagnula
Keyword(s):  
Intestinal Absorption ◽  
Absorption Enhancement ◽  
P Glycoprotein ◽  
In Situ Permeability ◽  
Glycoprotein Inhibition

scholarly journals Investigation of the Functional Role of P-Glycoprotein in Limiting the Oral Bioavailability of Lumefantrine

2013 ◽  
Vol 58 (1) ◽  
pp. 489-494 ◽  
Author(s):  
Wahajuddin ◽  
Kanumuri S. R. Raju ◽  
Sheelendra P. Singh ◽  
Isha Taneja
Keyword(s):  
Intestinal Absorption ◽  
Oral Absorption ◽  
Stability Study ◽  
Cytochrome P450 3A ◽  
Glycoprotein P ◽  
Active Efflux ◽  
P Glycoprotein

ABSTRACTIn the quest to explore the reason for the low and variable bioavailability of lumefantrine, we investigated the possible role of P-glycoprotein (P-gp) in lumefantrine intestinal absorption. Anin situsingle-pass intestinal perfusion study in rats with the P-gp inhibitor verapamil or quinidine and an ATPase assay with human P-gp membranes indicated that lumefantrine is a substrate of P-gp which limits its intestinal absorption. To confirm these findings, anin vivopharmacokinetic study was performed in rats. The oral administration of verapamil (10 mg/kg of body weight) along with lumefantrine caused a significant increase in its bioavailability with a concomitant decrease in clearance. The increase in bioavailability of lumefantrine could be due to inhibition of P-gp and/or cytochrome P450 3A in the intestine/liver by verapamil. However, in a rat intestinal microsomal stability study, lumefantrine was found to be resistant to oxidative metabolism. Further, anin situpermeation study clearly showed a significant role of P-gp in limiting the oral absorption of lumefantrine. Thus, the increase in lumefantrine bioavailability with verapamil is attributed in part to the P-gp-inhibitory ability of verapamil. In conclusion, lumefantrine is a substrate of P-gp, and active efflux by P-gp across the intestine partly contributed to the low/variable bioavailability of lumefantrine.

Comparison of the intestinal absorption and bioavailability of γ-tocotrienol and α-tocopherol: in vitro, in situ and in vivo studies

2012 ◽  
Vol 33 (5) ◽  
pp. 246-256 ◽  
Author(s):  
Bilal S. Abuasal ◽  
Hisham Qosa ◽  
Paul W. Sylvester ◽  
Amal Kaddoumi
Keyword(s):  
Intestinal Absorption ◽  
In Vivo Studies

99mTc-Sestamibi, A Sensitive Probe for In Vivo Imaging of P-Glycoprotein Inhibition by Modulators and mdr1 Antisense Oligodeoxynucleotides

2006 ◽  
Vol 8 (6) ◽  
pp. 333-339 ◽  
Author(s):  
Veronika Jekerle ◽  
Jing-Hung Wang ◽  
Deborah A. Scollard ◽  
Raymond M. Reilly ◽  
Michael Wiese ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Antisense Oligodeoxynucleotides ◽  
P Glycoprotein ◽  
Glycoprotein Inhibition ◽  
99Mtc Sestamibi

Intestinal absorption of hawthorn flavonoids – in vitro, in situ and in vivo correlations

Life Sciences ◽  
2006 ◽  
Vol 79 (26) ◽  
pp. 2455-2462 ◽  
Author(s):  
Zhong Zuo ◽  
Li Zhang ◽  
Limin Zhou ◽  
Qi Chang ◽  
Moses Chow
Keyword(s):  
Intestinal Absorption

Comparative Effects on Intestinal Absorption in Situ by P-glycoprotein-Modifying HIV Protease Inhibitors

2004 ◽  
Vol 21 (10) ◽  
pp. 1862-1866 ◽  
Author(s):  
Martin Richter ◽  
Nóra Gyémánt ◽  
Joséf Molnár ◽  
Andreas Hilgeroth
Keyword(s):  
Intestinal Absorption ◽  
Protease Inhibitors ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
P Glycoprotein

In vitro–in vivo correlation in p-glycoprotein mediated transport in intestinal absorption

2009 ◽  
Vol 36 (2-3) ◽  
pp. 200-211 ◽  
Author(s):  
Eva M. del Amo ◽  
Aki T. Heikkinen ◽  
Jukka Mönkkönen
Keyword(s):  
Intestinal Absorption ◽  
P Glycoprotein
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