Effect of topical application of diclofenac liposomal suspension on experimentally induced subcutaneous inflammation in horses

Fred J. CaldwellDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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P. O. Eric MuellerDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Randy C. LynnIDEXX Pharmaceuticals Inc, 4249 Piedmont Pkwy, Greensboro, NC 27410.

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Steven C. BudsbergDepartment of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Abstract

Objective—To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses.

Animals—7 healthy adult horses

Procedure—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 and Clinical Relevance—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. ( Am J Vet Res 2004;65:271–276)

Abstract

Objective—To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses.

Animals—7 healthy adult horses

Procedure—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 and Clinical Relevance—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. ( Am J Vet Res 2004;65:271–276)

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