American Journal of Animal and Veterinary Sciences 1 (1): 8-12, 2006 ISSN 1557-4555 © 2006 Science Publications Corresponding Author: María F. Landoni, Cátedra de Farmacología. Facultad de Ciencias Veterinarias. Universidad Nacional de La Plata. Calle 60 y 118 cc 296 (B1900AVW) La Plata. Argentina 8 Inefficacy of Topical Diclofenac in Arthritic Horses Nicolás F. Villarino , Tomas J. Vispo, Marcos, Ferrante and María F. Landoni Pharmacology Department. Faculty of Veterinary Science. University of La Plata Calle 60 y 118 cc 296 (B1900AVW) La Plata. Argentina Abstract: The objective of the present study was test the anti-inflammatory efficacy of diclofenac dietilamine, applied epicutaneously at a dose rate of 0.44 mg kg 1 , in a model of acute arthritis in horses. Four clinical end-points, as well as two biochemical markers, were used as surrogate markers of the required clinical response (analgesia, anti-inflammatory). Low diclofenac concentrations were measured in blood (C max 0.04±0.03 ug mL 1 ) and synovial fluid (C max 0.08 ±0.08 ug mL 1 ) from the first to the last sampling time. The statistical comparison of the clinical end-points and biochemical markers between placebo and dicilofenac treated group indicated a lack of pharmacological effect of this compound after epicutaneous administration. Key words: NSAIDs, horse, arthritis, diclofenac, transdermal INTRODUCTION Arthritis is the commonest joint disease in sport horses. Its therapy is directed towards the provision of analgesia, limitation of inflammation and limitation of the damage to joint tissues. Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used in horses for the treatment of pain and inflammation [1] . These drugs are usually administered orally or by injection. Although, systemic administration has many disadvantages such as, toxic effects (gastrointestinal and renal toxicity) mainly attributed to COX-1 inhibition. The treatment of a joint condition through topical drug administration led to better drug targeting, mainly, the synovial fluid [2,3] . Topical administration of NSAIDs provides the advantage of achieving a therapeutic effect without the risk of potential severe systemic side effects that may be associated with systemic administration. Diclofenac, a phenylacetic acid class NSAID, is an effective analgesic [4] , with potent COX inhibitory activity that is administered extensively for the treatment of various arthritic conditions in man [5] . However, there are not many reports about the anti- inflammatory effects of diclofenac in horses. In addition, the anti-inflammatory effects of diclofenac applied topically have not been studied in horses suffering acute arthritis. The effectiveness of a topical formulation depends on the ability of the formulation to dispense effective concentrations of drug at the biophase. The two major pathways of drug transport into and across skin are: (a) the transepidermal route across the stratum corneum and (b) the transfollicular route via the pilosebaceous units and shunts. Drug penetration could be affected by many factors including, skin thickness, chemical structure of the active principle, anatomical region and qualitative characteristic of the formulation [6-8] . These factors could modify the penetration of drugs through the skin determining the achievement of effective concentrations at the site of action, this situation being reflected in the clinical efficacy. In the present study, in order to evaluate the anti inflammatory effects of diclofenac administered epicutaneuosly, an experimental model of acute arthritis was used [1,9,10,11] . MATERIALS AND METHODS Experimental animals: Animals were six standard breed mares weighting 400 ± 20 kg. Inclusion criteria were over 2 year old, non-gestating mares, no previous joint inflammatory process and non-current or previous systemic immune disease. The animals were housed indoors in individual box stalls and fed a maintenance ration of hay twice daily. Water was freely available. The total surface of each carpal joint was established considering it as a cylinder (∅ x h). The calculated total surface of treatment was 450 cm 2 . (Circumference [∅]:30 cm and height [h]: 15 cm). All animal procedures were approved by the Secretaría de Ciencia y Técnica, Universidad Nacional de La Plata, Argentina. Experimental design and sampling procedures: Diclofenac diethylamine (Átomo Desinflamante®. IMVI. S.A Argentina) 1.16% (equivalent to 1g sodium diclofenac) was purchased to a local dealer. A two– period cross over Latin square design was used, such