Do formulation differences alter abuse liability of methylphenidate? A placebo-controlled, randomized, double-blind, crossover study in recreational drug users.

The primary objective of this study was to determine if the abuse liability of methylphenidate is governed by formulation differences that affect rates of drug delivery. In this double-blind, placebo-controlled, randomized, crossover study, subjects with a history of recreational drug use received single oral doses of placebo, 60 mg of immediate-release methylphenidate (IR) and 108 mg of extended-release methylphenidate (osmotic release oral system [OROS]). Over 24 hours after dosing, blood was collected to determine plasma concentrations of methylphenidate, and subjects completed subjective assessments of abuse liability (Addiction Research Center Inventory, Drug Rating Questionnaire-Subject, and Subjective Drug Value).

Potential interactions of methylphenidate and atomoxetine with dextromethorphan.

Objective: To examine the potential for drug-drug interactions to influence drug metabolism between the attention-deficit/hyperactivity disorder (ADHD) dl-methylphenidate and atomoxetine with dextromethorphan, a probe for interactions involving cytochrome P450 (CYP) 2D6 isoenzyme.

Design: In vitro and ex vivo analysis of changes in metabolism of study drugs.

Setting: Laboratory.

PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate.

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.

Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter, randomized prospective study.

This community-based study was designed to evaluate treatment outcomes with OROS methylphenidate (MPH) and atomoxetine in children with attentiondeficit/hyperactivity disorder (ADHD), as assessed by physicians and parents in a setting that resembles clinical practice. In a multicenter, prospective, open-label study, children 6 to 12 years of age with ADHD were randomized (2:1, respectively) to 3 weeks of treatment with once-daily OROS MPH or atomoxetine. Investigatorrated measures of symptoms included the ADHD Rating Scale (ADHD-RS) and the Clinical Global Impression-Improvement of Illness scale (CGI-I).

Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect.

The major human metabolite of atomoxetine (4-hydroxyatomoxetine) was tested against a panel of receptors and enzymes, and was found to interact with the mu, delta, and kappa-opioid receptors based upon studies involving both binding and functional assays. 4-hydroxyatomoxetine was determined to be a partial agonist of the kappa-opioid receptor.

Efficacy and Tolerability of Famotidine in Preventing Heartburn and Related Symptoms of Upper Gastrointestinal Discomfort.

This randomized, double-blind, placebo-controlled, four-way crossover trial was designed to compare the efficacy of famotidine and placebo in preventing meal-provoked upper gastrointestinal symptoms. One hundred twenty-one subjects (58 men and 63 women), aged 20--61 years, were randomly assigned to one of four treatment sequences which included single oral doses of placebo, famotidine 5 mg, famotidine 10 mg, and famotidine 20 mg, spaced approximately 7 days apart. To be eligible for randomization, subjects had to have at least a 2-month history of heartburn and acid/sour stomach occurring at least three times per week.