Effect of vehicles on percutaneous absorption of bucladesine (dibutyryl cyclic AMP) in normal and damaged rat skin.
Bucladesine, sodium N6,2'-O-dibutyryl cyclic 3',5' adenosine monophosphate (DBcAMP), which is effective for the treatment of chronic skin ulcers including decubitus ulcer, was evaluated for percutaneous absorption in rats with normal skin, stripped skin and full-thickness abrasion models. Percutaneous absorption from aqueous solution or ointment was very low in intact skin. When the aqueous solution was applied to the site where the skin had been excised, DBcAMP was absorbed very rapidly and almost completely. In the case of stripped skin, DBcAMP was absorbed rapidly but slower than in the full-thickness abrasion model. In both damages skin models, a better absorption profile was obtained with the polyethylene glycol (PEG) than the petrolatum ointment and DBcAMP was released continuously from the PEG ointment, indicating that this ointment is suitable for the treatment of ulcers of the skin. The percutaneous absorption from stripped skin was considerably influenced by the powder formulation. It is appropriate to evaluate the bioavailability in damaged skin models for a drug, such as DBcAMP, which is used in the treatment of skin ulcer.
Mafune
E
E
Pharmaceutical Formulation Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Takahashi
M
M
Takasugi
N
N
D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D003994:Bucladesine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D008297:Male; D009824:Ointments; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*
D009824:Ointments; D014677:Pharmaceutical Vehicles; D011208:Powders; D011092:Polyethylene Glycols; D003994:Bucladesine