Web Chapter 41 Pentoxifylline (PTX) is a methylxanthine derivative with multiple hemorheologic and immunomodulatory properties. PTX is available as a generic formulation or a brand name drug (Trental, 400-mg tablets). This drug has been used for almost 40 years in humans with intermittent claudication caused by peripheral and cerebrovascular atherosclerotic disease and for at least 10 years in veterinary medicine to treat a variety of conditions. The list of conditions for which PTX has been found to be potentially beneficial in dogs has grown rapidly (Marks et al, 2001). The drug is rarely used in feline dermatology (Nichols et al, 2001). This chapter reviews the use of PTX in small animal dermatology. PTX exerts multiple beneficial effects on the inflammatory cascade by increasing intracellular cAMP levels and decreasing synthesis of tumor necrosis factor-α (TNF-α). Since TNF-α is a proinflammatory cytokine with a broad spectrum of actions, its decrease leads to multiple antiinflammatory effects. These include decreased release of other proinflammatory cytokines such as interleukin-1 (IL-1) and IL-6, decreased leukocyte adhesion and aggregation, decreased neutrophil degranulation and superoxide release, inhibition of B-cell activation (by suppression of IL-6 synthesis), and inhibition of T-cell activation (through the CD23 and CD26 pathway) (Bruynzeel et al, 1995). Based on in vitro studies, the decrease of cytokine expression is dose dependent. The beneficial effects of PTX have been shown in numerous animal studies using models of ischemia-reperfusion and septic shock (Zhang et al, 1994). In these studies PTX significantly improved survival rates by both decreasing the inflammatory reaction and improving tissue oxygenation. Finally, PTX also improves wound healing by increasing fibroblast collagenases and decreasing collagen production, fibronectin, glycosaminoglycans, and fibroblast response to TNF-α. Canine familial dermatomyositis is an inflammatory disease in which microvascular vasculopathy is thought to play a role. Therefore dermatomyositis was one of the first dermatologic diseases in which PTX was tried and reported to have useful effects. In the management of dermatomyositis cases PTX usually is considered as a steroid-sparing agent and rarely as the only form of treatment (Rees et al, 2003). The advantage of using PTX is its better safety profile and lack of atrophogenic properties compared with glucocorticoids. The response to treatment is variable and typically slow (2 to 3 months). Historically a large range of dosages and treatment regimens have been suggested. Recommended dosage ranges from 10 to 20 mg/kg orally every 8 to 12 hours depending on the severity of the disease. Based on a study by Rees and Boothe (2003) it appears that a dosage of 25 mg/kg twice daily resulted in positive clinical response (four complete and six partial responses in the 10 dogs treated). In that study the authors investigated whether a direct correlation could be established between concentrations of PTX and its metabolites and clinical response; they concluded that, because of the variability in disposition and metabolite formation among individual dogs, monitoring of PTX concentration did not offer a therapeutic advantage.
Pentoxifylline
Properties of Pentoxifylline
Indications for Use in Veterinary Dermatology
Dermatomyositis
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