PET Study Examining Pharmacokinetics, Detection and Likeability, and Dopamine Transporter Receptor Occupancy of Short- and Long-Acting Oral Methylphenidate

Abstract

OBJECTIVE: The abuse potential of methylphenidate has been related to the drug’s capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would also produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate. METHOD: Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (Cmax) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses ...