Transdermal delivery of 5-fluorouracil through skin of hairless mice and humans in vitro: a comparison of the effect of formulations and a prodrug.
A 2% commercial solution formulation of 5-fluorouracil (5-FU) was significantly better at delivering 5-FU than either a 1% or 5% solution. Among single component suspension formulations the highest transdermal delivery was obtained from the vehicle in which 5-FU was least soluble, isopropyl myristate (IPM), while changes in the total suspended concentration of 5-FU in propyleneglycol (PG) had no significant effect on transdermal delivery by those suspensions. A prodrug of 5-FU/IPM was significantly better at delivering 5-FU than any of the formulations. The trends in relative rates of delivery of 5-FU by the formulations and the prodrug were the same in skin of hairless mice and humans. The mouse skin was about ten times more permeable than the human skin. Second application studies to assess skin damage caused by the formulations also showed the same trend in skin of hairless mice and humans: all of the formulations caused some damage.
Sherertz
E F
EF
Veterans Administration Medical Center (Research Service), Gainesville, Florida.
Sloan
K B
KB
McTiernan
R G
RG
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009226:Myristates / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009226:Myristates; D011355:Prodrugs; D011409:Propylene Glycols; C008205:isopropyl myristate; D019946:Propylene Glycol; D005472:Fluorouracil