Single- and Multiple-Dose Pharmacokinetics of an Oral Once-a-Day Osmotic Controlled-Release OROS® (methylphenidate HC1) Formulation

• Published in: Journal of clinical pharmacology 2000-04, Vol.40 (4), p.379-388
• Main Authors: Modi, Nishit B., Lindemulder, Betsy, Gupta, Suneel K.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adolescent; Adult; Area Under Curve; Biological and medical sciences; Biological Availability; Central Nervous System Stimulants - adverse effects; Central Nervous System Stimulants - metabolism; Central Nervous System Stimulants - pharmacokinetics; Cross-Over Studies; Delayed-Action Preparations; Dizziness - chemically induced; Dose-Response Relationship, Drug; Half-Life; Headache - chemically induced; Humans; Medical sciences; Methylphenidate - adverse effects; Methylphenidate - metabolism; Methylphenidate - pharmacokinetics; Middle Aged; Nausea - chemically induced; Neuropharmacology; Osmotic Pressure; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/00912700022009080

Methylphenidate is used for the treatment of attention deficit hyperactivity disorder (ADHD). OROS® (methylphenidate HCl) is an osmotic controlled‐release delivery system designed for once‐daily oral dosing. The pharmacokinetics of OROS® (methylphenidate HCl) 18 mg qd, sustained‐release (SR) methylphenidate 20 mg qd, and the immediate‐release (IR) formulation given as three 5 mg doses every 4 hours (tid) were compared in adults. In addition, the single‐ and multiple‐dose pharmacokinetics of the OROS® formulation were studied. Following OROS® (methylphenidate HCl), there was a gradual increase in the mean methylphenidate plasma concentrations with peak concentrations noted at 6 to 8 hours. With the SR formulation, peak plasma concentrations were noted at ∼4 hours. Following the IR regimen, methylphenidate plasma concentrations fluctuated in tandem with oral dosing; peak concentrations were noted at 6.5 hours. The terminal half‐life of methylphenidate was similar for the three formulations. The dose‐normalized methylphenidate Cmax for OROS® (methylphenidate HCl) was significantly lower than for IR and SR methylphenidate. The bioavailability of methylphenidate and PPA from OROS® (methylphenidate HCl) relative to the IR and SR formulations was complete. Mean methylphenidate AUC and terminal half‐life were similar after single (32.9 ng•h/mL and 3.9 hours) and multiple doses (35.2 ng•h/mL and 3.9 hours) of OROS® (methylphenidate HCl).