title: Novel bioequivalence approach for narrow therapeutic index drugs.
abstract: Narrow therapeutic index drugs are defined as those drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity. The US Food and Drug Administration proposes that the bioequivalence of narrow therapeutic index drugs be determined using a scaling approach with a four-way, fully replicated, crossover design study in healthy subjects that permits the simultaneous equivalence comparison of the mean and within-subject variability of the test and reference products. The proposed bioequivalence limits for narrow therapeutic index drugs of 90.00%-111.11% would be scaled based on the within-subject variability of the reference product. The proposed study design and data analysis should provide greater assurance of therapeutic equivalence of narrow therapeutic index drug products.
authors: Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors: L X
authors: LX
authors: Yu
authors: W
authors: W
authors: Jiang
authors: X
authors: X
authors: Zhang
authors: R
authors: R
authors: Lionberger
authors: F
authors: F
authors: Makhlouf
authors: D J
authors: DJ
authors: Schuirmann
authors: L
authors: L
authors: Muldowney
authors: M-L
authors: ML
authors: Chen
authors: B
authors: B
authors: Davit
authors: D
authors: D
authors: Conner
authors: J
authors: J
authors: Woodcock
mesh_terms: D006801:Humans; D055553:Prescription Drugs / Q000493:pharmacokinetics* / Q000592:standards*; D012107:Research Design / Q000592:standards*; D013223:Statistics as Topic / Q000592:standards*; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D055553:Prescription Drugs