Aem. Vickers et al., UPTAKE AND METABOLISM OF CYCLOSPORINE-A AND SDZ IMM-125 IN THE HUMAN IN-VITRO SKIN(2TM) DERMAL AND BARRIER FUNCTION MODELS, Life sciences, 57(3), 1995, pp. 215-224
Citations number
23
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
Treatment of psoriasis with the immunosuppressant cyclosporin A (CSA)
is beneficial orally but topical treatment is less efficacious. A comp
arison of CSA to its hydroxyethyl derivative SDZ IMM 125 (IMM) as to b
ioavailability to epidermal and dermal cells and the potential for ina
ctivation by biotransformation was investigated using a human dermal s
kin model (skin(2)(TM) ZK1100) and a barrier function model (skin(2)(T
M) ZK1300). The dermal ZK1100 model demonstrated that both cyclosporin
s could be metabolized by human dermis to the known primary hydroxylat
ed metabolite, M17/AM1 for CSA and the hydroxylated analogue of IMM, I
MM1. Application of the cyclosporins to the stratum corneum of the bar
rier function model ZK1300 demonstrated that both CSA and IMM would be
bioavailable to the epidermal and dermal skin cells. Systemic concent
rations would be expected to be low due to the slow permeation of the
compounds and because mostly metabolites would reach the circulation.
The difference between the two cyclosporins was the rate and extent of
biotransformation with IMM metabolite formation being about 1/4 that
of GSA.