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).
- Clinical pharmacokinetics
- Drug interactions
- Mechanism based inhibition
Yubero-Lahoz, S., Pardo, R., Farre, M., Mathuna, B. Ó., Torrens, M., Mustata, C., Perez-Mañá, C., Langohr, K., Carbó, M. L., & de la Torre, R. D. L. (2012). Changes in CYP1A2 activity in humans after 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) administration using caffeine as a probe drug. Drug Metabolism and Pharmacokinetics, 27(6), 605-613. https://doi.org/10.2133/dmpk.DMPK-12-RG-032