In vivo percutaneous absorption of [14C]acitretin in the hairless guinea pig and in the rhesus monkey.
The oral administration of retinoids such as etretinate and acitretin (Ro 10-1670, CAS 55079-83-9), provides a successful therapeutic approach in various cutaneous diseases characterized by disturbed keratinization, e.g. psoriasis. Nevertheless oral therapy is often associated with systemic adverse effects. This makes a topical form with no or reduced systemic side effects desirable. Direct application of a topical acitretin formulation to the skin might result in therapeutic skin concentrations while minimizing systemic exposure. In the hairless guinea pig and in the rhesus monkey the percutaneous absorption of [14C]acitretin from an isopropylmyristate formulation (160 micrograms acitretin/2.5 cm2/animal) were investigated in vivo. After a 24 h exposure drug concentration in the skin was higher in the hairless guinea pig (620 ng-eq/g wet tissue) than in the rhesus monkey (380 ng-eq/g wet tissue). A similar observation was made comparing the 24 h absorption data determined as amount of drug excreted. The results are compared with in vitro absorption data using skin from the same species.
Surber
C
C
Department of Dermatology, University of California, San Francisco.
Wilhelm
K P
KP
Maibach
H I
HI
D017255:Acitretin / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008253:Macaca mulatta; D012869:Skin Absorption
D017255:Acitretin