PMID- 26395866
OWN - NLM
STAT- MEDLINE
DCOM- 20160818
LR  - 20151028
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 43
IP  - 12
DP  - 2015 Dec
TI  - Chiral Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine and its Phase 
      I and II Metabolites following Controlled Administration to Humans.
PG  - 1864-71
LID - 10.1124/dmd.115.066340 [doi]
AB  - Generally, pharmacokinetic studies on 3,4-methylenedioxymethamphetamine (MDMA) in 
      blood have been performed after conjugate cleavage, without taking into account 
      that phase II metabolites represent distinct chemical entities with their own 
      effects and stereoselective pharmacokinetics. The aim of the present study was to 
      stereoselectively investigate the pharmacokinetics of intact glucuronide and 
      sulfate metabolites of MDMA in blood plasma after a controlled single MDMA dose. 
      Plasma samples from 16 healthy participants receiving 125 mg of MDMA orally in a 
      controlled study were analyzed using liquid chromatography-tandem mass 
      spectroscopy after chiral derivatization. Pharmacokinetic parameters of R- and 
      S-stereoisomers were determined. Sulfates of 3,4-dihydroxymethamphetamine (DHMA), 
      and sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA) were 
      identified, whereas free phase I metabolites were not detected. Stereoselective 
      differences in Cmax and AUC24 were observed with the following preferences: R>S 
      for MDMA and DHMA 4-sulfate; S>R for 3,4-methylenedioxyamphetamine (MDA), DHMA 
      3-sulfate, and HMMA glucuronide; and no preference in Cmax for HMMA sulfate. R/S 
      ratios were >1 for all analytes after 24 hours, independent of the initial chiral 
      preference. These are the first data on chiral pharmacokinetics of MDMA phase II 
      metabolites in human plasma in vivo after controlled administration. The main 
      human MDMA metabolites were shown to be sulfate and glucuronide conjugates.
CI  - Copyright (c) 2015 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Steuer, Andrea E
AU  - Steuer AE
AD  - Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic 
      Medicine, University of Zurich, Switzerland (A.E.S, C.S., T.K.); Division of 
      Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of 
      Clinical Research, University Hospital Basel, Switzerland (Y.S., A.R., M.E.L.) 
      andrea.steuer@irm.uzh.ch.
FAU - Schmidhauser, Corina
AU  - Schmidhauser C
AD  - Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic 
      Medicine, University of Zurich, Switzerland (A.E.S, C.S., T.K.); Division of 
      Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of 
      Clinical Research, University Hospital Basel, Switzerland (Y.S., A.R., M.E.L.).
FAU - Schmid, Yasmin
AU  - Schmid Y
AD  - Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic 
      Medicine, University of Zurich, Switzerland (A.E.S, C.S., T.K.); Division of 
      Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of 
      Clinical Research, University Hospital Basel, Switzerland (Y.S., A.R., M.E.L.).
FAU - Rickli, Anna
AU  - Rickli A
AD  - Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic 
      Medicine, University of Zurich, Switzerland (A.E.S, C.S., T.K.); Division of 
      Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of 
      Clinical Research, University Hospital Basel, Switzerland (Y.S., A.R., M.E.L.).
FAU - Liechti, Matthias E
AU  - Liechti ME
AD  - Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic 
      Medicine, University of Zurich, Switzerland (A.E.S, C.S., T.K.); Division of 
      Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of 
      Clinical Research, University Hospital Basel, Switzerland (Y.S., A.R., M.E.L.).
FAU - Kraemer, Thomas
AU  - Kraemer T
AD  - Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic 
      Medicine, University of Zurich, Switzerland (A.E.S, C.S., T.K.); Division of 
      Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of 
      Clinical Research, University Hospital Basel, Switzerland (Y.S., A.R., M.E.L.).
LA  - eng
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150922
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 117652-28-5 (4-hydroxy-3-methoxymethamphetamine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*administration & dosage/*blood/chemistry
MH  - Administration, Oral
MH  - Adult
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Methamphetamine/administration & dosage/*analogs & derivatives/blood/chemistry
MH  - Stereoisomerism
MH  - Young Adult
EDAT- 2015/09/24 06:00
MHDA- 2016/08/19 06:00
CRDT- 2015/09/24 06:00
PHST- 2015/07/16 00:00 [received]
PHST- 2015/09/21 00:00 [accepted]
PHST- 2015/09/24 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/08/19 06:00 [medline]
AID - dmd.115.066340 [pii]
AID - 10.1124/dmd.115.066340 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2015 Dec;43(12):1864-71. doi: 10.1124/dmd.115.066340. Epub 
      2015 Sep 22.