Differences in the In Vitro and In Vivo Pharmacokinetic Profiles of Once-Daily Modified-Release Methylphenidate Formulations in Canada: Examination of Current Bioequivalence Criteria

Abstract Background Current Canadian bioequivalence criteria rely on rate and extent of drug exposure, that is, Cmax and AUC. In the case of complex modified-release formulations, these criteria may not address pharmacokinetic differences with potential therapeutic and tolerability implications. Obj...

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Bibliographic Details
Published in:Clinical therapeutics 2012-05, Vol.34 (5), p.1170-1181
Main Authors: Shram, Megan J., PhD, Quinn, Anne Marie, MSc, Chen, Nancy, PhD, Faulknor, Janice, MD, Luong, Doanh, MSc, Sellers, Edward M., MD, PhD, Endrenyi, Laszlo, PhD
Format: Article
Language:English
Subjects:
Adult
Area Under Curve
Bioequivalence
Biological and medical sciences
Canada
Central Nervous System Stimulants - administration & dosage
Central Nervous System Stimulants - pharmacokinetics
Complex modified-release formulation
Confidence intervals
Cross-Over Studies
Delayed-Action Preparations
Drug dosages
Drug therapy
Female
Generic products
Humans
In vitro dissolution
Internal Medicine
Male
Medical Education
Medical sciences
Methylphenidate
Methylphenidate - administration & dosage
Methylphenidate - pharmacokinetics
Osmotic Pressure
Partial area under the concentration-time curve
Pharmacokinetics
Pharmacology. Drug treatments
Plasma
Regulatory approval
Solubility
Studies
Tablets
Therapeutic Equivalency
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Summary:Abstract Background Current Canadian bioequivalence criteria rely on rate and extent of drug exposure, that is, Cmax and AUC. In the case of complex modified-release formulations, these criteria may not address pharmacokinetic differences with potential therapeutic and tolerability implications. Objective This study was performed to characterize in vitro dissolution and in vivo pharmacokinetic profiles of three modified-release formulations of methylphenidate (MPH) marketed in Canada, two of which meet the criteria for assuming bioequivalence as defined by Health Canada: MPH extended-release (ER-C) and osmotic controlled-release oral-delivery-system (OROS-MPH). Methods In vitro dissolution tests were performed using 54-mg OROS-MPH, 54-mg MPH ER-C, and 20-mg MPH sustained-release (SR) tablets. In vivo pharmacokinetics of single oral doses of 54 mg OROS-MPH, 54 mg MPH ER-C, and 60 mg MPH-SR were evaluated in an open-label, randomized, crossover study in healthy subjects. Plasma samples were collected up to 24 hours after administration of the drug. Results In vitro dose-corrected release profiles of MPH ER-C and MPH-SR tablets were similar (
ISSN:0149-2918
1879-114X
DOI:10.1016/j.clinthera.2012.02.010