PMID- 21446053
OWN - NLM
STAT- MEDLINE
DCOM- 20111004
LR  - 20221207
IS  - 1099-081X (Electronic)
IS  - 0142-2782 (Linking)
VI  - 32
IP  - 4
DP  - 2011 May
TI  - Induction of drug efflux protein expression by venlafaxine but not 
      desvenlafaxine.
PG  - 233-44
LID - 10.1002/bdd.753 [doi]
AB  - Venlafaxine and its metabolite desvenlafaxine are serotonin-norepinephrine 
      reuptake inhibitors currently prescribed for the treatment of depression. 
      Previously, it was reported that venlafaxine is an inducer of MDR1, the gene 
      responsible for P-glycoprotein (P-gp). The present study expanded upon these 
      findings by examining the effect of venlafaxine and desvenlafaxine on the 
      expression of both P-gp and the breast cancer resistance protein (BCRP) in human 
      brain endothelial cells (HBMEC), an in vitro model of the blood-brain barrier 
      (BBB). The HBMEC were treated for 1 h with various concentrations (500 nM to 
      50 microM) of venlafaxine and desvenlafaxine. Western blot analysis revealed 
      treatment with venlafaxine significantly induced the expression of P-gp (2-fold) 
      and BCRP (1.75-fold) in a dose-dependent manner, while treatment with 
      desvenlafaxine had no effect on drug efflux transporter expression. To determine 
      the functional significance of this effect, the permeability of a known drug 
      efflux probe, rhodamine 123, across the BBB model and Caco-2 cells, a model of 
      intestinal absorption, were examined. Treatment with venlafaxine (1-50 microM) for 
      1 h significantly reduced the apical-to-basolateral permeability of R123 across 
      the BBB model (30%) and Caco-2 cell monolayers (25%), indicative of increased 
      drug efflux transporter expression at the apical membrane. Conversely, 
      desvenlafaxine had no effect on R123 permeability in either cellular model. These 
      studies indicate that venlafaxine, but not desvenlafaxine is an inducer of drug 
      efflux transporter expression, which consequently increases the potential for 
      clinical drug-drug interactions. Therefore, based on these preliminary results, 
      caution should be taken when prescribing venlafaxine with other P-gp substrates.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Bachmeier, Corbin J
AU  - Bachmeier CJ
AD  - The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA.
FAU - Beaulieu-Abdelahad, David
AU  - Beaulieu-Abdelahad D
FAU - Ganey, Nowell J
AU  - Ganey NJ
FAU - Mullan, Michael J
AU  - Mullan MJ
FAU - Levin, Gary M
AU  - Levin GM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110328
PL  - England
TA  - Biopharm Drug Dispos
JT  - Biopharmaceutics & drug disposition
JID - 7911226
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Cyclohexanols)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 1N3CZ14C5O (Rhodamine 123)
RN  - 7D7RX5A8MO (Venlafaxine Hydrochloride)
RN  - VJT6J7R4TR (Rifampin)
RN  - ZB22ENF0XR (Desvenlafaxine Succinate)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - ATP-Binding Cassette Transporters/biosynthesis/drug effects
MH  - Biological Transport
MH  - Blood-Brain Barrier/*drug effects
MH  - Brain/*drug effects/metabolism
MH  - Caco-2 Cells
MH  - Cell Membrane Permeability/drug effects
MH  - Cells, Cultured
MH  - Cyclohexanols/*pharmacology/toxicity
MH  - Desvenlafaxine Succinate
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Endothelial Cells
MH  - Enzyme Inhibitors/pharmacology
MH  - Fluorescent Dyes/metabolism
MH  - Humans
MH  - Intestinal Absorption/drug effects
MH  - Neoplasm Proteins/biosynthesis/drug effects
MH  - Rhodamine 123/pharmacokinetics
MH  - Rifampin/pharmacology
MH  - Selective Serotonin Reuptake Inhibitors/*pharmacology/toxicity
MH  - Venlafaxine Hydrochloride
EDAT- 2011/03/30 06:00
MHDA- 2011/10/05 06:00
CRDT- 2011/03/30 06:00
PHST- 2010/09/03 00:00 [received]
PHST- 2011/02/01 00:00 [revised]
PHST- 2011/02/13 00:00 [accepted]
PHST- 2011/03/30 06:00 [entrez]
PHST- 2011/03/30 06:00 [pubmed]
PHST- 2011/10/05 06:00 [medline]
AID - 10.1002/bdd.753 [doi]
PST - ppublish
SO  - Biopharm Drug Dispos. 2011 May;32(4):233-44. doi: 10.1002/bdd.753. Epub 2011 Mar 
      28.