title: Dose-proportional pharmacokinetics of d-threo-methylphenidate after a repeated-action release dosage form.
abstract: A bimodal extended-release formulation of d-methylphenidate (d-MPH) has been developed to enable fast onset of action and once-daily administration in patients with attention deficit hyperactivity disorder. The authors studied the dose proportionality of extended-release d-MPH pharmacokinetics. Twenty-five healthy adult volunteers received 5, 10, 20, 30, and 40 mg d-MPH in a crossover study with 7 days between doses. All doses were well tolerated. Dose proportionality was shown for all dose-dependent pharmacokinetic parameters. Geometric means (%gCV) for the first Cmax peak, Cmax0-4, were 3.25 (29.0%), 6.05 (27.1%), 12.6 (31.9%), 18.5 (31.9%), and 25.2 ng/mL (29.3%) for d-MPH 5, 10, 20, 30, and 40 mg, respectively. Geometric means (%gCV) for Cmax4-10 were 3.18 (27.5%), 5.84 (27.7%), 12.5 (31.7%), 17.7 (31.6%), and 23.6 ng/mL (29.0%), respectively. Geometric means for AUC(0-infinity) were 24.3 (30.7%), 45.9 (30.2%), 96.4 (35.5%), 144 (33.3%), and 195 ng x h/mL (30.9%), respectively. The pharmacokinetics of once-daily extended-release d-MPH are proportional to the dose.
authors.affiliation: Novartis Pharma AG, Lichtstrasse 35, CH-4002 Basel, Switzerland.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Tuerck
authors.forename: Silke
authors.initials: S
authors.lastname: Appel-Dingemanse
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Maboudian
authors.forename: Francoise
authors.initials: F
authors.lastname: Pommier
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
authors.forename: Greg
authors.initials: G
authors.lastname: Sedek
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D015259:Dopamine Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D015259:Dopamine Agents; D008774:Methylphenidate