Binding of prednisolone and its ester prodrugs in the skin.
OBJECTIVE
Skin binding of prednisolone and its esters was investigated in the hairless mouse skin in vitro.


METHODS
The distribution of the amount of drugs bound in the skin was determined by a skin slicing technique. The model drugs used were prednisolone (PN, M.W. 360) and its esters, senesyonate (PN-C5, M.W. 442), geranate (PN-C10, M.W. 510), farnesylate (PN-C15, M.W. 578), and geranylgeranate (PN-C20, M.W. 646).


RESULTS
The distribution of bound drug was nonhomogeneous in the skin; the concentration of PN-C10 and PN-C15 in the skin increased gradually with the distance from the skin surface. The parent drug, PN, however, was hardly bound in the viable skin.


CONCLUSIONS
These findings suggest that the prodrugs of prednisolone may prolong the dermal retention of the parent drug and minimize to delivery into the systemic circulation of the prodrug and metabolite.
Hikima
T
T
Department of Biochemical Science and Engineering, College of Computer Science and Biosystems Engineering, Kyushu Institute of Technology, Fukuoka, Japan.
Tojo
K
K
D000818:Animals; D001711:Biotransformation; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004952:Esters; D005260:Female; D007531:Isoflurophate / Q000494:pharmacology; D051379:Mice; D011239:Prednisolone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000378:metabolism* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D004952:Esters; D011355:Prodrugs; D007531:Isoflurophate; D011239:Prednisolone