Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products.
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.
Department of Dermatology, University of Utah, Salt Lake City, 84132, USA. pershing@derm.med.utah.edu
Lynn K
LK
Pershing
Joel L
JL
Nelson
Judy L
JL
Corlett
Surendra P
SP
Shrivastava
Don B
DB
Hare
Vinod P
VP
Shah
D000287:Administration, Topical; D000328:Adult; D001706:Biopsy; D005260:Female; D005782:Gels; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000166:cytology; D013048:Specimen Handling; D013810:Therapeutic Equivalency; D014212:Tretinoin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D005782:Gels; D007641:Keratolytic Agents; D014212:Tretinoin; D015474:Isotretinoin