Lipophilic metronidazole derivatives and their absorption through hairless mouse skin.
Previously we have shown that the diacyl glyceryl ester of naproxen is absorbed into excised mouse skin and slowly degraded to release naproxen. In the present work we have synthesised some organic acid and fatty acid derivatives of metronidazole, and studied the in-vitro degradation in aqueous buffer solutions and serum as well as their permeation through hairless mouse skin. The derivatives were enzymatically degraded in serum to form metronidazole. Only the acetic acid and butyric acid derivatives were able to permeate hairless mouse skin intact. The fatty acid derivatives released metronidazole within the skin. The metronidazole delivery through the skin was significant when the metronidazole oleate was used. This compound could therefore be considered as a suitable pro drug for dermal applications.
Másson
M
M
Department of Pharmacy, University of Iceland, Reykjavík, Iceland. mmasson@rhi.hi.is
Thorsteinsson
T
T
Sigurdsson
T H
TH
Loftsson
T
T
D000287:Administration, Topical; D000818:Animals; D000994:Antitrichomonal Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002021:Buffers; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005227:Fatty Acids / Q000737:chemistry; D005260:Female; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D008809:Mice, Inbred C3H; D012869:Skin Absorption
D000994:Antitrichomonal Agents; D002021:Buffers; D005227:Fatty Acids; D008795:Metronidazole