PMID- 16552717
OWN - NLM
STAT- MEDLINE
DCOM- 20061114
LR  - 20181201
IS  - 0142-2782 (Print)
IS  - 0142-2782 (Linking)
VI  - 27
IP  - 5
DP  - 2006 Jul
TI  - Apparent active transport of MDMA is not mediated by P-glycoprotein: a comparison 
      with MDCK and Caco-2 monolayers.
PG  - 219-27
AB  - Amphetamines and their methylenedioxy derivatives generically display similar 
      behavioral, physiologic and toxic effects. Inconsistent pharmacokinetic and 
      toxicity data for methylenedioxymethamphetamine (MDMA) may suggest that active 
      drug transporters are interacting with these compounds, and thus altering drug 
      absorption and tissue distribution. In vitro models of CNS accumulation and 
      intestinal drug transport were used to assess efflux transport of MDMA. 
      Madin-Darby kidney cell epithelial (MDCK) monolayers displayed a 4-fold increase 
      in accumulation in the basolateral to apical orientation relative to the apical 
      to basolateral orientation, although no differential accumulation was noted 
      between MDCK-WT and MDCK-MDR1 monolayers. Caco-2 monolayers demonstrated an 
      approximate 2-fold increase in accumulation of MDMA. Exposure of various 
      inhibitors of active drug transporters demonstrated mixed results; ritonavir, 
      progesterone and indomethacin produced an approximately 50% reduction of MDMA 
      transport, while verapamil, MK-571 and probenecid had no effect. Based on these 
      data, it is concluded that MDMA efflux is mediated via the activity of a 
      transporter distinct from P-glycoprotein. The possible inhibitory effects of 
      amphetamines on rhodamine-123 transport were also assessed. MDMA, 
      methylenedioxyamphetamine, amphetamine and methamphetamine, at physiologically 
      relevant concentrations, did not significantly alter the transport of 
      rhodamine-123 in Caco-2 monolayers or the LS180 cell line, suggesting that these 
      compounds do not alter the function of P-glycoprotein.
CI  - Copyright 2006 John Wiley & Sons, Ltd.
FAU - Bertelsen, Kirk M
AU  - Bertelsen KM
AD  - Department of Pharmacology and Experimental Therapeutics, Tufts University School 
      of Medicine, Boston, MA 02111, USA.
FAU - Greenblatt, David J
AU  - Greenblatt DJ
FAU - von Moltke, Lisa L
AU  - von Moltke LL
LA  - eng
GR  - AG-17880/AG/NIA NIH HHS/United States
GR  - AI-58784/AI/NIAID NIH HHS/United States
GR  - AT-01381/AT/NCCIH NIH HHS/United States
GR  - DA-05258/DA/NIDA NIH HHS/United States
GR  - DA-13209/DA/NIDA NIH HHS/United States
GR  - DK-13834/DK/NIDDK NIH HHS/United States
GR  - DK-58496/DK/NIDDK NIH HHS/United States
GR  - MH-58435/MH/NIMH NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Biopharm Drug Dispos
JT  - Biopharmaceutics & drug disposition
JID - 7911226
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Propionates)
RN  - 0 (Quinolines)
RN  - 1N3CZ14C5O (Rhodamine 123)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 5Q9O54P0H7 (verlukast)
RN  - CJ0O37KU29 (Verapamil)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - O3J8G9O825 (Ritonavir)
RN  - PO572Z7917 (Probenecid)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & 
      inhibitors/*metabolism
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Caco-2 Cells
MH  - Cell Line
MH  - Dogs
MH  - Humans
MH  - Indomethacin/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*metabolism
MH  - Probenecid/pharmacology
MH  - Progesterone/pharmacology
MH  - Propionates/pharmacology
MH  - Quinolines/pharmacology
MH  - Rhodamine 123/metabolism
MH  - Ritonavir/pharmacology
MH  - Verapamil/pharmacology
EDAT- 2006/03/23 09:00
MHDA- 2006/11/15 09:00
CRDT- 2006/03/23 09:00
PHST- 2006/03/23 09:00 [pubmed]
PHST- 2006/11/15 09:00 [medline]
PHST- 2006/03/23 09:00 [entrez]
AID - 10.1002/bdd.501 [doi]
PST - ppublish
SO  - Biopharm Drug Dispos. 2006 Jul;27(5):219-27. doi: 10.1002/bdd.501.