PMID- 20008456
OWN - NLM
STAT- MEDLINE
DCOM- 20100416
LR  - 20191210
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 114
IP  - 1
DP  - 2010 Mar
TI  - Population pharmacokinetics of 3,4-methylenedioxymethamphetamine and main 
      metabolites in rats.
PG  - 38-47
LID - 10.1093/toxsci/kfp300 [doi]
AB  - The pharmacokinetics of the recreational drug 3,4-methylenedioxymethamphetamine 
      (MDMA) and its mains metabolites have never been modeled together. We therefore 
      designed a model with which to analyze the pharmacokinetics of MDMA, 
      3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 
      and 4-hydroxy-3-methoxyamphetamine (HMA) and to test the effect of covariates 
      like gender and body weight on the pharmacokinetics. Rats (18 males and 18 
      females) were given 1 mg/kg MDMA iv, and the concentrations of MDMA, MDA, and 
      HMMA were measured by high-performance liquid chromatography-mass spectrometry. 
      Another 30 rats (15 males) were given 1 mg/kg MDA, and MDA and HMA were measured. 
      A population pharmacokinetic model was developed to describe the changes in MDMA, 
      HMMA, MDA, and HMA concentrations over time and to estimate interanimal 
      variability. The influence of gender was tested using a likelihood ratio test. 
      Estimated exposures of males and females to MDMA and its metabolites were 
      compared using the Wilcoxon nonparametric test. An integrated six-compartment 
      model adequately described the data. MDMA (two compartments) was transformed 
      irreversible to HMMA (one compartment) and MDA (two compartments), which then 
      produced HMA (one compartment). All rate constants were first order. Females 
      given MDMA had significantly smaller MDMA distribution volumes than males, and 
      they converted less MDMA to MDA than did males. Our MDMA, MDA, HMA, and HMMA 
      model is suitable for examining the relationship between drug concentrations and 
      its pharmacological/toxicological effects. Male rats were exposed to 
      significantly more MDA and HMA than were females, which could explain why males 
      are more sensitive to MDMA toxic effects than females.
FAU - Hirt, Deborah
AU  - Hirt D
AD  - Faculte de Pharmacie, Universite Paris Descartes, Paris F-75006, France. 
      deborah.hirt@parisdescartes.fr
FAU - Fonsart, Julien
AU  - Fonsart J
FAU - Menet, Marie-Claude
AU  - Menet MC
FAU - Debray, Marcel
AU  - Debray M
FAU - Noble, Florence
AU  - Noble F
FAU - Decleves, Xavier
AU  - Decleves X
FAU - Scherrmann, Jean-Michel
AU  - Scherrmann JM
LA  - eng
PT  - Journal Article
DEP - 20091214
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Illicit Drugs)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Female
MH  - Illicit Drugs/*pharmacokinetics
MH  - Male
MH  - Models, Animal
MH  - Models, Chemical
MH  - N-Methyl-3,4-methylenedioxyamphetamine/analogs & 
      derivatives/metabolism/*pharmacokinetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sex Factors
EDAT- 2009/12/17 06:00
MHDA- 2010/04/17 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
AID - kfp300 [pii]
AID - 10.1093/toxsci/kfp300 [doi]
PST - ppublish
SO  - Toxicol Sci. 2010 Mar;114(1):38-47. doi: 10.1093/toxsci/kfp300. Epub 2009 Dec 14.