title: Open Flow Microperfusion as a Dermal Pharmacokinetic Approach to Evaluate Topical Bioequivalence.
abstract: The availability of generic topical dermatological drug products is constrained by the limited methods established to assess topical bioequivalence (BE). A novel cutaneous pharmacokinetic approach, dermal open-flow microperfusion (dOFM), can continuously assess the rate and extent to which a topical drug becomes available in the dermis, to compare in vivo dermal bioavailability (BA) and support BE evaluations for topical products.
  
  
  
  To evaluate whether dOFM is an accurate, sensitive, and reproducible in vivo method to characterize the intradermal BA of acyclovir from 5 % acyclovir creams, comparing a reference (R) product either to itself or to a different test (T) product.
  
  
  
  In a single-center clinical study, R or T products were applied to six randomized treatment sites on the skin of 20 healthy human subjects. Two dOFM probes were inserted in each treatment site to monitor the intradermal acyclovir concentration for 36 h. Comparative BA (of R vs. R and T vs. R) was evaluated based on conventional BE criteria for pharmacokinetic endpoints (area under the curve and maximum dermal concentration) where the 90 % confidence interval of the geometric mean ratio between the T and R falls within 0.80-1.25.
  
  
  
  The positive control products (R vs. R) were accurately and reproducibly confirmed to be bioequivalent, while the negative control products (T vs. R) were sensitively discriminated not to be bioequivalent.
  
  
  
  dOFM accurately, sensitively, and reproducibly characterized the dermal BA in a manner that can support BE evaluations for topical acyclovir 5 % creams in a study with n = 40 (20 subjects in this study).
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
authors.forename: Manfred
authors.initials: M
authors.lastname: Bodenlenz
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
authors.forename: Katrin I
authors.initials: KI
authors.lastname: Tiffner
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
authors.forename: Reingard
authors.initials: R
authors.lastname: Raml
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Augustin
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Dragatin
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Birngruber
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
authors.forename: Denise
authors.initials: D
authors.lastname: Schimek
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schwagerle
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.|Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: Division of Therapeutic Performance, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Sam G
authors.initials: SG
authors.lastname: Raney
authors.affiliation: Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.|Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: Isadore
authors.initials: I
authors.lastname: Kanfer
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010, Graz, Austria. frank.sinner@joanneum.at.|Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. frank.sinner@joanneum.at.
authors.forename: Frank
authors.initials: F
authors.lastname: Sinner
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods*; D063465:Skin Cream / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir