title: Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation.
abstract: Amphetamine (AMP) salts-based extended-release (ER) drug products are widely used for the treatment of attention deficit hyperactivity disorder. We developed physiologically based absorption models for mixed AMP salts ER capsules and dextroamphetamine sulfate ER capsules to address specific questions raised during generic drug postmarketing surveillance and bioequivalence (BE) guidance development. The models were verified against several data sets. Virtual BE simulations were conducted to assess BE in various populations other than normal healthy subjects where BE studies are generally conducted for approval. The models were also used to predict pharmacokinetics (PK) for hypothetical formulations having dissolution profiles falling within specification after the development of in vitro-in vivo relation. Finally, we demonstrated how to use the models to test sensitivity of PK metrics to the changes in formulation variables.
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Babiskin
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000661:Amphetamine / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D003913:Dextroamphetamine / Q000493:pharmacokinetics; D004341:Drug Evaluation / Q000379:methods; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D012492:Salts / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D016568:Drugs, Generic; D012492:Salts; D000661:Amphetamine; D003913:Dextroamphetamine
keywords: absorption; bioavailability; bioequivalence; clinical trial simulation; modified release; physiological model