MDMA pharmacokinetics: A population and physiologically based pharmacokinetics model-informed analysis.
CPT: pharmacometrics & systems pharmacology February 1, 2025 Marilyn A Huestis, William B Smith, Cathrine Leonowens et al. 3 citations
MDMA (midomafetamine) is being reviewed by the FDA to treat post-traumatic stress disorder. A phase I study found that a high-fat/high-calorie meal did not change MDMA plasma concentrations, only delayed the time to reach peak concentration. A population pharmacokinetic model showed no meaningful effects from age, weight, sex, race, or fed status. A physiologically based pharmacokinetic model predicted that splitting the clinical dose (120 or 180 mg MDMA HCl) into two doses two hours apart results in slightly lower early exposure and a delayed peak compared to a single dose. The model also confirmed MDMA is a strong inhibitor of CYP2D6 but does not meaningfully affect drugs cleared by renal transporters.