Role of P-Glycoprotein and Cytochrome P450 3A in Limiting Oral Absorption of Peptides and Peptidomimetics†

1998 ◽  
Vol 87 (11) ◽  
pp. 1322-1330 ◽  
Author(s):  
Vincent J. Wacher ◽  
Jeffrey A. Silverman ◽  
Yuanchao Zhang ◽  
Leslie Z. Benet
Keyword(s):  
Cytochrome P450 ◽  
Oral Absorption ◽  
Cytochrome P450 3A ◽  
P Glycoprotein

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.

Pharmacogenetics of Clozapine: In Vivo Role of Cytochrome P450 Isoforms and P-Glycoprotein

2008 ◽  
Vol 41 (05) ◽  
Author(s):  
E Jaquenoud-Sirot ◽  
B Knezevic ◽  
G Perla Morena ◽  
P Baumann ◽  
CB Eap
Keyword(s):  
Cytochrome P450 ◽  
P Glycoprotein ◽  
Cytochrome P450 Isoforms

scholarly journals P-glycoprotein and cytochrome P450 3A act together in restricting the oral bioavailability of paclitaxel

2012 ◽  
Vol 132 (10) ◽  
pp. 2439-2447 ◽  
Author(s):  
Jeroen J.M.A. Hendrikx ◽  
Jurjen S. Lagas ◽  
Hilde Rosing ◽  
Jan H.M. Schellens ◽  
Jos H. Beijnen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Oral Bioavailability ◽  
Cytochrome P450 3A ◽  
P Glycoprotein

Effect of genistein on the activities of cytochrome P450 3A and P-glycoprotein in Chinese healthy participants

Xenobiotica ◽  
2011 ◽  
Vol 42 (2) ◽  
pp. 173-178 ◽  
Author(s):  
C.-Q. Xiao ◽  
R. Chen ◽  
J. Lin ◽  
G. Wang ◽  
Y. Chen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A ◽  
P Glycoprotein ◽  
Healthy Participants
Sign in / Sign up

Export Citation Format

Share Document