Changes in CYP1A2 activity in humans after 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) administration using caffeine as a probe drug

Samanta Yubero-Lahoz, Ricardo Pardo, Magí Farre, Brian Ó Mathuna, Marta Torrens, Cristina Mustata, Clara Perez-Mañá, Klaus Langohr, Marcel lí Carbó, Rafael D.L. de la Torre

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13 Citations (Scopus)

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6, and is also a potent mechanism-based inhibitor of the enzyme. After assessing the inhibition and recovery of CYP2D6 in a previous study, the aim of this work was to study in humans the activity of CYP1A2 in vivo after CYP2D6 had been inhibited by MDMA, using caffeine as a probe drug. Twelve male and nine female recreational MDMA users were included. In session 1, 100 mg of caffeine was given at 0 h. In session 2, a 1.5mg/kg MDMA dose (range 75100mg) was given at 0 h followed by a 100 mg dose of caffeine 4 h later. Aliquots of plasma were assayed for caffeine (137X) and paraxanthine (17X) and statistically significant differences were assessed with a one-way ANOVA. There were significant gender differences at basal condition, which persisted after MDMA administration. CYP1A2 activity was higher in both genders after drug administration, with an increase in 40% in females and 20% in males. Results show an increase in CYP1A2 activity when CYP2D6 is inhibited by MDMA in both genders, being more pronounced in females. © 2012 by the Japanese Society for the Study of Xenobiotics (JSSX).
Original languageEnglish
Pages (from-to)605-613
JournalDrug Metabolism and Pharmacokinetics
Volume27
Issue number6
DOIs
Publication statusPublished - 1 Jan 2012

Keywords

  • Caffeine
  • Clinical pharmacokinetics
  • CYP1A2
  • CYP2D6
  • Drug interactions
  • MDMA
  • Mechanism based inhibition

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