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dc.contributor.authorDas, Sharmila
dc.date.accessioned2020-08-11T15:21:09Z
dc.date.available2020-08-11T15:21:09Z
dc.date.issued2020en_US
dc.identifier.urihttp://hdl.handle.net/10713/13510
dc.description2020
dc.descriptionPharmaceutical Sciences
dc.descriptionUniversity of Maryland, Baltimore
dc.descriptionPh.D.
dc.description.abstractThe objective of this dissertation is to assess the bioequivalence of generic drugs. Patients with epilepsy complain about more seizures and side effects after brand-generic or generic-generic switching of an anti-epileptic drug (AED). Generic brittleness (GB) is the familiar notion that, upon switching between AEDs of pharmaceutical equivalents, a patient experiences negative outcome. Aim 1 is to probe the individual patient attributes thought to predispose a patient to generic brittleness. At the University of Maryland Medical Center, 148 patients from the outpatient epilepsy clinic were recruited for an observational case-control study. An algorithm for being GB (40% of patients) and not GB was devised. A patient with epilepsy was categorized as GB if the patient negatively opined about generics and was taking brand of their most problematic AED when generic was available. Two demographic factors that increased the odds of being GB were a patient currently taking a problem AED and increasing total number of current medications. Interestingly, taking lamotrigine increased and taking any one of six “protective” anti-epileptic drugs decreased the odds of being GB, respectively. Furthermore, no genetic, clinical laboratory or neuropsychiatry tests or their sub-elements differentiated GB patients from not GB patients. Aim 2 involves a comparative pharmacokinetic (PK) analysis upon challenging sixteen GB patients to brand-generic or generic-generic switch of an AED that they are currently on, using a four-way crossover replicate design. For each patient, test and reference PK profiles were the same, despite patients being GB. Aim 3 is to assess the noninferiority of the generic sodium ferric gluconate (SFG) against the reference product Ferrlecit with respect to drug bound iron (DBI), after single dose intravenous administration of brand and generic SFG in 44 healthy volunteers. Using a two-way crossover replicate design, plasma PK profiles of SFG to Ferrlecit were the same across two iron species (e.g. DBI and NTBI), although adverse event rates differed. In conclusion generics of AEDs and intravenous sodium ferric gluconate are bioequivalent to the brand-name drugs. Results support FDA criteria for bioequivalence in regards to AEDs and complex iron products.
dc.subjectanti-epileptic drugs
dc.subjectnoninferiorityen_US
dc.subjectsodium ferric gluconateen_US
dc.subjectsubstitutionen_US
dc.subjectswitchingen_US
dc.subject.meshAnticonvulsantsen_US
dc.subject.meshDrugs, Genericen_US
dc.subject.meshTherapeutic Equivalencyen_US
dc.titleEvaluation of the Equivalency of Generic Drugsen_US
dc.typedissertationen_US
dc.date.updated2020-08-07T19:03:58Z
dc.language.rfc3066en
dc.contributor.advisorPolli, James E.
refterms.dateFOA2020-08-11T15:21:10Z


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