Adapalene 0.1% gel and adapalene 0.1% cream stimulate retinoic acid receptor mediated gene transcription without significant irritative effects in the skin of healthy human volunteers.
A randomized, investigator masked, intra individual comparative study was conducted in 30 healthy volunteers to compare the cutaneous effects of adapalene 0.1% gel and adapalene 0.1% cream with their respective vehicles, using tretinoin 0.05% cream (n = 21) or tretinoin 0.1% cream (n = 9) and a tretinoin cream vehicle (n = 30) as controls. The products were applied to hip/buttock skin for 4 days under occlusive conditions. Cytosolic retinoic acid binding protein-II (CRABP-II) mRNA levels were measured using the RT-PCR technique in punch biopsies taken from 10 subjects. Epidermal thickness was assessed using image analysis of haematoxylin and eosin stained sections from another 11 subjects. Erythema was assessed in all subjects both by a visual scoring system and by chromameter. Adapalene 0.1% gel and adapalene 0.1% cream produced similar significant increases in CRABP-II mRNA levels compared to their vehicles (P < 0.01). The two tretinoin formulations also resulted in similar significant increases in CRABP-II compared to the cream vehicle (P < 0.001). However, only the two tretinoin formulations resulted in an increase in epidermal thickness and only the tretinoin 0.1% cream resulted in significant erythema. Adapalene 0.1% gel and adapalene 0.1% cream induce RAR-mediated gene expression to a similar degree in this model, without the irritant effects of tretinoin.
Griffiths
C E
CE
Section of Dermatology, University of Manchester, Hope Hospital, UK.
Ancian
P
P
Humphries
J
J
Poncet
M
M
Rizova
E
E
Michel
S
S
Clucas
A
A
D000068816:Adapalene; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004890:Erythema / Q000139:chemically induced; D005782:Gels; D006801:Humans; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D009824:Ointments; D018168:Receptors, Retinoic Acid / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology