Griseofulvin
Griseofulvin is the only antifungal approved for systemic administration by the FDA for veterinary use. Griseofulvin is a metabolite of P. griseofulvum, P. janczewski, and P. patulum that inhibits cell wall synthesis.
It binds to tubulin and thereby induces conformational changes in the alpha and beta subunits. Indirectly, it causes an impaired processing of newly synthesized cell wall constituents at the growing tips of hyphae (De Carli and Larizza 1988). Griseofulvin mainly concentrates in keratinocytes; therefore, it is only used for noninvasive dermatophyte infections (Lewis 2011).Overall, dermatophytes (Microsporum spp., Trichophyton spp., and Epidermophyton) are susceptible to griseofulvin; however it is not active against yeasts (Malassezia and Candida). Since the late 1950s, griseofulvin has been the gold standard for the systemic therapy of human tinea capitis (Shemer et al. 2013). However, the advent of newer antifungals that exhibit more favorable pharmacokinetic and toxicity profiles has largely relegated griseofulvin to a second-line agent against dermatophytoses in humans. The main disadvantage of griseofulvin is the long duration of treatment that is required (6-12 weeks or longer), which may lead to reduced compliance (Elewski 1999). Another challenge is the high expense of griseofulvin because of the large quantity of drug required for a cure. Moreover, the efficacy of griseofulvin has decreased in recent years owing to decreased susceptibility of the infective fungi due to changes in epidemiology and mutations (Chen and Friedlander 2001), resulting in a need for larger doses and longer treatment durations.
Griseofulvin is licensed for treatment of dermatophytosis in dogs and cats (Medleau and Whiteweithers 1992; Moriello and Deboer 1995) and is still widely used in some countries. It is administered orally for at least 4-6 weeks at 25-50 mg/ kg q12-24 h with a fatty meal to increase absorption. Adverse reactions include anorexia, vomiting, diarrhea, and bone marrow suppression, particularly in Siamese, Himalayan, and Abyssinian cats. The use of griseofulvin is contraindicated in kittens younger than 6 weeks of age and in pregnant animals as the compound is teratogenic, particularly during the first weeks of gestation (Frymus et al. 2013).
In ruminants, griseofulvin formulations as powder or as granules mixed into the feed have been used for the treatment of dermatophytosis (Andrews and Edwardson 1981; Power and Malone 1987). Long-term treatment with griseofulvin is shown to be effective against T. equinum ringworm in horses (Plumb 1999). Equine sporotrichosis has also been successfully cured with griseofulvin (Fishburn and Kelley 1967; Greydanus-van der Putten et al. 1994). Oral griseofulvin may also be prescribed for rabbits, rodents, and fur animals (Rochette et al. 2003).