Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products

J Am Acad Dermatol. 2003 May;48(5):740-51. doi: 10.1067/mjd.2003.175.

Abstract

Background: A new dermatopharmacokinetic (DPK) approach has been proposed for bioequivalence determination of topical drug products by comparing the drug content kinetics in stratum corneum.

Objective: We sought to establish any correlation between clinical safety/efficacy and DPK approach in bioequivalence determination of tretinoin gel 0.025%.

Methods: Tretinoin and isotretinoin were quantified in human volar forearm stratum corneum as a function of time with 3 tretinoin gel 0.025% products in 49 patients. Stratum corneum layers were harvested using multiple adhesive disks, which were subsequently extracted and quantified for both isomers by high-performance liquid chromatography.

Results: Products with similar composition and therapeutic equivalence were found bioequivalent, and products with different composition and clinical profiles were found bioinequivalent by DPK methodology.

Conclusions: There is a direct correlation between DPK parameters in healthy patients and clinical safety/efficacy of tretinoin gel products in patients with acne. Data support the use of DPK parameters and methodology in the bioequivalence assessment of topical tretinoin gel products.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Topical
  • Adult
  • Biopsy
  • Female
  • Gels
  • Humans
  • Isotretinoin / administration & dosage
  • Isotretinoin / pharmacokinetics*
  • Keratolytic Agents / administration & dosage
  • Keratolytic Agents / pharmacokinetics*
  • Male
  • Middle Aged
  • Skin / cytology
  • Specimen Handling
  • Therapeutic Equivalency
  • Tretinoin / administration & dosage
  • Tretinoin / pharmacokinetics*

Substances

  • Gels
  • Keratolytic Agents
  • Tretinoin
  • Isotretinoin