Effect of topical application of diclofenac liposomal suspension on experimentally induced subcutaneous inflammation in horses.
OBJECTIVE
To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses.


METHODS
7 healthy adult horses.


METHODS
Inflammation was produced by injecting 1% sterile carrageenan into subcutaneously implanted tissue cages 8 hours before (time -8) and at the time of application of test ointment. A crossover design was used. Horses received 1 of 2 treatments (topically administered control or DLS ointments) during 48 hours of carrageenan-induced subcutaneous inflammation. A single application of test ointment (7.2 g) was applied over each tissue cage (time 0). Samples of transudate and blood were collected at -8, 0, 6, 12, 18, 24, 30, 36, and 48 hours. Plasma and transudate diclofenac concentrations were determined by use of high-performance liquid chromatography. Transudate concentrations of prostaglandin E2 (PGE2) were determined with a competitive enzyme immunoassay.


RESULTS
DLS was absorbed transdermally. The highest concentration (mean +/- SEM, 76.2 +/- 29 ng/mL) was detectable in tissue-cage fluid within 18 hours after application. Minimal concentrations of diclofenac were detectable in plasma. Application of DLS significantly decreased transudate concentrations of PGE2 at 6 and 30 hours. Decreases in PGE2 concentration were observed in the DLS group at all collection times.


CONCLUSIONS
A single topical application of DLS resulted in concentrations of diclofenac in transudate within 6 hours and significantly attenuated carrageenan-induced local production of PGE2. Results of this study suggest that DLS is readily absorbed transdermally and may be efficacious for reducing subcutaneous inflammation in horses.
Caldwell
Fred J
FJ
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Mueller
P O Eric
PO
Lynn
Randy C
RC
Budsberg
Steven C
SC
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage* / Q000627:therapeutic use*; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000188:drug therapy / Q000662:veterinary; D008081:Liposomes; D040521:Subcutaneous Tissue
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008081:Liposomes; D004008:Diclofenac; D002351:Carrageenan