title: Bioequivalence of Sandoz methylphenidate osmotic-controlled release tablet with Concerta® (Janssen-Cilag).
abstract: The aim was to assess the bioequivalence of Sandoz methylphenidate osmotic-controlled release (OCR) tablets (Sandoz [Methylphenidate[ MPH OCR) with Concerta®, a methylphenidate formulation indicated for the treatment of attention deficit/hyperactivity disorder (ADHD). Four open-label, randomized, single-dose, two-way crossover bioequivalence studies were conducted in healthy subjects: three fasting studies with 54-, 36- and 18-mg doses of methylphenidate, and one fed study with the 54-mg dose. The d- and l-threo-methylphenidate plasma levels were quantified using liquid chromatographic methods with tandem mass spectrometry (LC MS/MS). Bioequivalence of the formulations was accepted if the 90% geometric confidence intervals of the ratio of least-squares means of Sandoz MPH OCR to Concerta® of ln-transformed area under the curve (AUC0-t ) and C max were within the acceptance range of 80-125%. All studies met the bioequivalence criteria, and 90% geometric confidence intervals for AUC0-t and C max were within the predefined range. All plasma concentration time curves for Sandoz MPH OCR under fasting conditions showed a biphasic profile comparable with Concerta®, confirmed by bioequivalence of the partial metrics AUC0-2h, AUC2-24 h, C max(0-2 h) and C max(2-24 h). Both products were well tolerated and no relevant differences in the safety profiles were observed. It was concluded that Sandoz MPH OCR is bioequivalent to Concerta® in terms of rate and extent of absorption when administered as a single dose of one extended-release tablet of 54, 36, or 18 mg under fasting conditions and at a dose of 54 mg under fed conditions.
authors.affiliation: Sandoz Development Center Holzkirchen Holzkirchen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schapperer
authors.affiliation: Sandoz Development Center Holzkirchen Holzkirchen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Daumann
authors.affiliation: inVentiv Health Clinical Montréal, Quebec, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lamouche
authors.affiliation: Sandoz Development Center Holzkirchen Holzkirchen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Thyroff-Friesinger
authors.affiliation: inVentiv Health Clinical Montréal, Quebec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Viel
authors.affiliation: Center of Drug Absorption and Transport, Institute of Pharmacy, University of Greifswald Greifswald, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Weitschies
keywords: ADHD; Concerta®; Sandoz; bioequivalence; extended release; methylphenidate; osmotic-controlled release