Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine After Controlled Oral Administration to Young Adults
- 1 June 2008
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Therapeutic Drug Monitoring
- Vol. 30 (3), 320-332
- https://doi.org/10.1097/ftd.0b013e3181684fa0
Abstract
This study examines the plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) in young adults for up to 143 hours after drug administration. Seventeen female and male participants (black, white, and Hispanic) received placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral MDMA doses (comparable to recreational doses) in a double-blind, randomized, balanced, within-subject design while residing on a closed research unit. Doses were separated by 1 week or more. A fully validated two-dimensional gas chromatography/mass spectrometry method simultaneously quantified MDMA, HMMA, MDA, and HMA. Calibration curves were MDA, 1 to 100 ng/mL; HMA, 2.5 to 100 ng/mL; and MDMA and HMMA, 2.5 to 400 ng/mL. Mean ± standard deviation maximum plasma concentrations (Cmax) of 162.9 ± 39.8 and 171.9 ± 79.5 ng/mL were observed for MDMA and HMMA, respectively, after low-dose MDMA. After the high dose, mean MDMA Cmax significantly increased to 291.8 ± 76.5 ng/mL, whereas mean HMMA Cmax was unchanged at 173.5 ± 66.3 ng/mL. High intersubject variability in Cmax was observed. Mean MDA Cmax were 8.4 ± 2.1 (low) and 13.8 ± 3.8 (high) ng/mL. HMA Cmax were 3.5 ± 0.4 and 3.9 ± 0.9 ng/mL after the low and high doses, respectively. AUC∞ displayed similar trends to Cmax, demonstrating nonlinear pharmacokinetics. Times of last plasma detection were generally HMA < MDA < MDMA < HMMA. Mean half-lives (t1/2) of MDMA, MDA, and HMMA were approximately 7 to 8 hours, 10.5 to 12.5 hours, and 11.5 to 13.5 hours, respectively. HMA t1/2 showed high variability. Mean MDMA volume of distribution was constant for low and high doses; clearance was significantly higher after the low dose. This study presents MDMA plasma pharmacokinetic data for the first time from blacks and females as well as measurement of HMMA and HMA concentrations after low and high MDMA doses and more frequent and extended plasma sampling than in prior studies.Keywords
This publication has 60 references indexed in Scilit:
- Influence of CYP2D6 polymorphism on 3,4-methylenedioxymethamphetamine (‘Ecstasy’) cytotoxicityPharmacogenetics and Genomics, 2006
- Intravascular Ecstasy: An Unusual Cause of Thigh Compartment SyndromeThe Journal of Trauma and Acute Care Surgery, 2006
- Severe Ecstasy poisoning in a toddlerAnaesthesia, 2006
- CYP2D6 genetic variation in healthy adults and psychiatric African-American subjects: implications for clinical practice and genetic testingThe Pharmacogenomics Journal, 2006
- MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stressJournal of Psychopharmacology, 2006
- The varieties of ecstatic experience: an exploration of the subjective experiences of ecstasyJournal of Psychopharmacology, 2006
- Contribution ???of ???Cytochrome??? P450??2D6??to??3,4-Methylenedioxymethamphetamine Disposition in HumansClinical Pharmacokinetics, 2005
- MECHANISM-BASED INACTIVATION OF CYP2D6 BY METHYLENEDIOXYMETHAMPHETAMINEDrug Metabolism and Disposition, 2004
- The Influence of Sex on PharmacokineticsClinical Pharmacokinetics, 2003
- Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy VolunteersNeuropsychopharmacology, 1998