Griseofulvin is a systemic antifungal agent that is effective against the common dermatophytes. It is practically insoluble in water and only slightly soluble in most organic solvents. Particle sizes of griseo-fulvin vary from 2.7 μm (ultramicrosized) to 10 μm (microsized).

Antifungal Activity

Mode of Action

Dermatophytes concentrate griseofulvin by an energy-dependent process. The drug then disrupts the mitotic spindle by interacting with the polymerized microtubules in susceptible dermatophytes. This leads to the production of multinucleate fungal cells. The inhibition of nucleic acid synthesis and the formation of hyphal cell wall material may also be involved. The result is distortion, irregular swelling, and spiral curling of the hyphae. Griseofulvin is fungistatic rather than fungicidal, except in young active cells.

Fungal Resistance

Dermatophytes can be made resistant to griseofulvin in vitro.

Antifungal Spectra

Griseofulvin is active against Microsporum, Epidermophyton, and Trichophyton spp. It has no effect on bacteria (including Actinomyces and Nocardia spp), other fungi, or yeasts.

Pharmacokinetic Features

Absorption

Plasma levels peak in ~4 hr after administration PO, but absorption from the GI tract continues over a prolonged period. Absorption is highly variable and is influenced by a number of factors. The rates of disaggregation and dissolution in the GI tract limit the bioavailability of griseofulvin; thus, microsized and ultramicrosized particles are usually used. High-fat meals, margarine, or propylene glycol significantly enhance GI absorption of griseofulvin and are indicated if the microsized particles are used.

Distribution

Griseofulvin is deposited in keratin precursor cells within 4–8 hr of administration PO. Sweat and transdermal fluid loss appear to play an important role in griseofulvin transfer in the stratum corneum. When these cells differentiate, griseofulvin remains bound and persists in keratin, making it resistant to fungal invasion. For this reason, new growth of hair, nails, or horn is the first to become free of fungal infection. As the fungus-containing keratin is shed, it is replaced by normal skin and hair. Only a small fraction of a dose of griseofulvin remains in the body fluids or tissues.

Biotransformation and Pharmacokinetics

Depending on the species, 10–50% of a griseofulvin dose is excreted almost exclusively as metabolites in the urine, and the remainder in the feces for ~4–5 days after administration. The elimination half-life of griseofulvin is ~24 hr in several species. The drug can be detected in 48–72 hr at the base level of the skin, in 6–12 days in the lower quarter, and in 2–19 days in the middle section of the horny layer.

Therapeutic Indications and Dose Rates

Griseofulvin is used for dermatophyte infections in dogs, cats, calves, horses, and other domestic and exotic animal species. Most dermatophytes are sensitive, but certain species present greater therapeutic challenges than others. Several may require higher dose rates for satisfactory control.

General dosages for griseofulvin are listed in see Antifungal Agents: Dosages of Griseofulvin. The dose rate and frequency should be adjusted as needed for the individual animal.

Table 3
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Dosages of Griseofulvin Species Dosage, Route, and Frequency Dogs, cats Microsized: 10–30 (up to 130) mg/kg, PO, sid or divided bid-tid; Ultramicrosized: 5–10 (up to 50) mg/kg, PO, sid Horses, cattle 5–10 mg/kg, PO, sid for 3–6 wk, or longer if required

Special Clinical Concerns

Adverse Effects and Toxicity

Adverse effects induced by griseofulvin are rare. Nausea, vomiting, and diarrhea have been seen. Hepatotoxicity has also been reported. Animals with impaired liver function should not be given griseofulvin because its biotransformation will be reduced and toxic levels may be reached. Idiosyncratic toxicity in cats has been reported. Griseofulvin is contraindicated in pregnant animals (especially mares and queens) because it is teratogenic.

Interactions

Lipids increase the GI absorption of griseofulvin. Barbiturates decrease its absorption and antifungal activity. Griseofulvin is a microsomal enzyme inducer and promotes the biotransformation of many concurrently administered drugs. The combined use of ketoconazole and griseofulvin may lead to hepatotoxicity.

Effects on Laboratory Tests

Alkaline phosphatase, AST, and ALT increase. Proteinuria may be detected.

Last full review/revision March 2012 by Dawn Merton Boothe, DVM, PhD, DACVIM, DACVCP