Transdermal absorption of radioprotectors in the rat using permeation-enhancing vehicles.
Topical radioprotection of rat skin with WR-2721 has not been effective presumably because the drug does not cross the stratum corneum to reach the epidermis and dermis. Earlier, we showed in the mouse that WR-2721 and cysteine dissolved in permeation-enhancing vehicles passed through the skin more readily than when in water. However, the most effective vehicles in the mouse were not necessarily as effective in the rat. Here we report that the most effective transport vehicles in the rat were (1) water with WR-2721, (2) water and dimethylformamide (DMF) with cysteine, and (3) water and DMF with prostaglandin E2 (PGE2). Pretreatment of the skin with dimethylsulfoxide (DMSO) further improved the transfer of the radioprotectors across the skin in most cases. After pretreatment with DMSO, the most effective vehicles were (1) water for WR-2721, (2) water and methyl-2-pyrrolidone (M-2-P) for cysteine, and (3) DMF for PGE2.
Lamperti
A
A
Department of Anatomy, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Ziskin
M C
MC
Bergey
E
E
Gorlowski
J
J
Sodicoff
M
M
D004999:Amifostine / Q000493:pharmacokinetics; D000818:Animals; D003545:Cysteine / Q000493:pharmacokinetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004126:Dimethylformamide / Q000494:pharmacology; D015232:Dinoprostone / Q000493:pharmacokinetics; D005260:Female; D011837:Radiation-Protective Agents / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption / Q000187:drug effects*; D014867:Water / Q000008:administration & dosage
D011837:Radiation-Protective Agents; D014867:Water; D004126:Dimethylformamide; D015232:Dinoprostone; D003545:Cysteine; D004999:Amifostine; D004121:Dimethyl Sulfoxide