title: Use of excised human skin to assess the bioequivalence of topical products.
abstract: BACKGROUND
  Establishing the bioequivalence of topical drug products is a costly and time-consuming process since, with few exceptions, clinical efficacy trials are required.
  
  
  OBJECTIVE
  To develop a surrogate for clinical bioequivalence testing through evaluation of the kinetics of drug absorption in vitro through excised human skin.
  
  
  METHODS
  The percutaneous absorption of seven approved generic topical drug products was compared with their corresponding reference products during preclinical development using the Franz diffusion cell. Thereafter, following the conduct of bioequivalence trials and regulatory approval of these products in the United States, clinical data became available to which the in vitro data were compared.
  
  
  RESULTS
  In six of the seven cases the in vitro test:reference ratio for total absorption was close to one and indicated that the products were equivalent, in agreement with the clinical data. Results from the seventh case, in which the test:reference ratio was only 0.63, indicated that the in vitro model actually had greater sensitivity than the clinical method to detect small differences between products.
  
  
  CONCLUSIONS
  These data demonstrate the relevance and predictive power of the in vitro human skin model and strongly support its use as a surrogate for in vivo bioequivalence studies.
authors.affiliation: Cetero Research, Fargo, North Dakota, USA. franzcell@verizon.net
authors.forename: T J
authors.initials: TJ
authors.lastname: Franz
authors.forename: P A
authors.initials: PA
authors.lastname: Lehman
authors.forename: S G
authors.initials: SG
authors.lastname: Raney
mesh_terms: D000287:Administration, Topical; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D012189:Retrospective Studies; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*; D013810:Therapeutic Equivalency
chemical_list: D004364:Pharmaceutical Preparations
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